Regulation of myocardial growth and death by GSK-3

Summary

Principal Investigator: Junichi Sadoshima
Abstract: DESCRIPTION (provided by applicant): Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, plays an important role in regulating growth and death of cardiomyocytes. During the current funding cycle, we established that GSK-3 is a negative regulator of cardiac hypertrophy and has substantial influence on cardiac function when its activity is modulated by phosphorylation during hypertrophy and heart failure (HF). Furthermore, our recent study conducted using GSK-3a(S21A) and GSK-3b(S9A) knock-in (KI) mice demonstrated that GSK-3 has isoform specific functions, which may be attributed to the distinct subcellular localizations of GSK-3a and GSK-3b. Unexpectedly, S21 phosphorylation of GSK-3a and S9 phosphorylation GSK-3b exhibited opposite functional consequences in the heart under pressure overload, indicating the importance of re-evaluating the function of the GSK-3 isoforms with special emphasis on their subcellular localization and unique targets. Thus, one important theme in this proposal is to demonstrate that endogenous GSK-3a and GSK-3b, localized in different subcellular locations/compartments, play distinct roles in mediating growth, death and differentiation of cardiomyocytes and their precursor cells. In particular, we will elucidate the isoform-specific functions of GSK-3 during pressure overload-induced cardiac hypertrophy, ischemia/reperfusion (I/R) and differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) by focusing on novel connections between GSK-3 isoforms and their downstream targets. Our hypotheses are: 1. GSK-3a, primarily localized in the nucleus, regulates expression of E2F in adult hearts. Phosphorylation of GSK-3a and subsequent upregulation of E2F is a compensatory mechanism to supplement myocyte proliferation and prevent mitochondrial dysfunction during pressure overload. 2. GSK-3b regulates survival and death of cardiomyocytes during I/R. Activation of GSK-3b during ischemia inhibits mTOR through a TSC2-dependent mechanism, stimulates autophagy, and protects the heart from cell death. On the other hand, phosphorylation/inactivation of GSK-3b during reperfusion is beneficial through activation of mTOR. 3. Upregulation of GSK-3b and downregulation of GSK- 3a facilitate differentiation of BM-derived MSCs into the cardiomyocyte lineage through distinct molecular mechanisms. Injection of MSCs in which GSK-3b is upregulated and GSK-3a is downregulated ex vivo facilitates the recovery of the heart after myocardial infarction (MI) through stimulation of cardiomyocyte differentiation and angiogenesis. We will address these issues, using genetically altered mouse models and integrated molecular and physiological approaches. Our study will elucidate the isoform-specific functions and unique downstream targets of GSK-3a and GSK-3b in mediating both growth/death and differentiation in the heart under stresses. The knowledge obtained from this investigation will lead to a better understanding of the molecular mechanisms mediating HF, ischemic injury, and stem cell differentiation, which can be utilized to develop specific interventions to treat HF and ischemic heart disease, and improve cell-based therapies. PUBLIC HEALTH RELEVANCE: Despite recent progress in medical therapy, heart failure is one of the most common causes of death in western countries. Understanding the molecular mechanism mediating growth and death of cardiac muscle is fundamentally important and potentially leads to better medical treatment for heart failure. This laboratory has been working on an enzyme termed glycogen synthase kinase-3, which plays an essential role in regulating growth and death of cardiomyocytes. Although this enzyme in the heart exists as two distinct forms, namely alpha and beta isoforms, the function of each form is not well understood. We will investigate the function of each isoform during heart failure, ischemic heart disease and stem cell differentiation, using genetically modified mice and mouse models of heart failure and ischemia/reperfusion injury. The knowledge obtained from this investigation should be useful for the development of better treatment for heart failure, ischemic injury and stem cell therapy.
Funding Period: 2000-09-30 - 2013-06-30
more information: NIH RePORT

Top Publications

  1. pmc Thioredoxin 1 negatively regulates angiotensin II-induced cardiac hypertrophy through upregulation of miR-98/let-7
    Yanfei Yang
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, NJ 07103, USA
    Circ Res 108:305-13. 2011
  2. pmc Redox modification of cell signaling in the cardiovascular system
    Dan Shao
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    J Mol Cell Cardiol 52:550-8. 2012
  3. pmc PPARα-Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcriptional pathway
    Shinichi Oka
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Cell Metab 14:598-611. 2011
  4. pmc Glycogen synthase kinase-3β controls autophagy during myocardial ischemia and reperfusion
    Peiyong Zhai
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
    Autophagy 8:138-9. 2012
  5. pmc Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome
    Sebastiano Sciarretta
    Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Medical Science Building, Newark, NJ 07103, USA
    Circulation 125:1134-46. 2012
  6. pmc Suppression of ERR targets by a PPARα/Sirt1 complex in the failing heart
    Shin ichi Oka
    University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
    Cell Cycle 11:856-64. 2012
  7. pmc Angiotensin II and oxidative stress in the failing heart
    Daniela Zablocki
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey
    Antioxid Redox Signal 19:1095-109. 2013
  8. pmc Protection of the heart against ischemia/reperfusion by silent information regulator 1
    Takanobu Yamamoto
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    Trends Cardiovasc Med 21:27-32. 2011
  9. pmc Comparative analysis of mRNA isoform expression in cardiac hypertrophy and development reveals multiple post-transcriptional regulatory modules
    Ji Yeon Park
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America
    PLoS ONE 6:e22391. 2011
  10. pmc Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion
    Peiyong Zhai
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 109:502-11. 2011

Detail Information

Publications95

  1. pmc Thioredoxin 1 negatively regulates angiotensin II-induced cardiac hypertrophy through upregulation of miR-98/let-7
    Yanfei Yang
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, NJ 07103, USA
    Circ Res 108:305-13. 2011
    ..Thioredoxin (Trx)1 inhibits pathological cardiac hypertrophy. MicroRNAs (miRNAs) are small noncoding RNAs that downregulate posttranscriptional expression of target molecules...
  2. pmc Redox modification of cell signaling in the cardiovascular system
    Dan Shao
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    J Mol Cell Cardiol 52:550-8. 2012
    ..Finally, we will discuss some techniques applied to monitoring redox status and identifying redox-sensitive proteins in the heart. This article is part of a Special Section entitled "Post-translational Modification."..
  3. pmc PPARα-Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcriptional pathway
    Shinichi Oka
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Cell Metab 14:598-611. 2011
    ..These results suggest that suppression of the ERR transcriptional pathway by PPARα/Sirt1, a physiological fasting response, is involved in the progression of heart failure by promoting mitochondrial dysfunction...
  4. pmc Glycogen synthase kinase-3β controls autophagy during myocardial ischemia and reperfusion
    Peiyong Zhai
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
    Autophagy 8:138-9. 2012
    ..Here we discuss the role of GSK-3β in mediating autophagy in the heart...
  5. pmc Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome
    Sebastiano Sciarretta
    Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Medical Science Building, Newark, NJ 07103, USA
    Circulation 125:1134-46. 2012
    ..Rheb is a GTP-binding protein that promotes cell survival and mediates the cellular response to energy deprivation (ED). The role of Rheb in the regulation of cell survival during ED has not been investigated in the heart...
  6. pmc Suppression of ERR targets by a PPARα/Sirt1 complex in the failing heart
    Shin ichi Oka
    University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
    Cell Cycle 11:856-64. 2012
    ..These results suggest that PPARα and Sirt1 downregulate ERR target gene expression through direct interaction with the ERRE in the failing heart...
  7. pmc Angiotensin II and oxidative stress in the failing heart
    Daniela Zablocki
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey
    Antioxid Redox Signal 19:1095-109. 2013
    ..As a result, investigation of the mechanisms involved in the development of HF continues to be an active field of study...
  8. pmc Protection of the heart against ischemia/reperfusion by silent information regulator 1
    Takanobu Yamamoto
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    Trends Cardiovasc Med 21:27-32. 2011
    ..Here, we discuss the cardioprotective effects of Sirt1 and possible underlying mechanisms...
  9. pmc Comparative analysis of mRNA isoform expression in cardiac hypertrophy and development reveals multiple post-transcriptional regulatory modules
    Ji Yeon Park
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America
    PLoS ONE 6:e22391. 2011
    ....
  10. pmc Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion
    Peiyong Zhai
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 109:502-11. 2011
    ..Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated...
  11. pmc Distinction of thioredoxin transnitrosylation and denitrosylation target proteins by the ICAT quantitative approach
    Changgong Wu
    Center for Advanced Proteomics Research and Department of Biochemistry and Molecular Biology, UMDNJ New Jersey Medical School Cancer Center, Newark, NJ 07103, USA
    J Proteomics 74:2498-509. 2011
    ..Unexpectedly, we found that many nitrosylation sites are reversibly regulated by Trx1, suggesting a more prominent role for Trx1 in regulating S-nitrosylation...
  12. pmc The NADPH oxidase Nox4 and aging in the heart
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    Aging (Albany NY) 2:1012-6. 2010
    ..This raises an intriguing possibility that Nox4 may play an important role in mediating aging of the heart. Here we discuss the potential involvement of Nox4 in mitochondrial oxidative stress and aging in the heart...
  13. pmc Regulation of myocardial growth and death by NADPH oxidase
    Yasuhiro Maejima
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    J Mol Cell Cardiol 50:408-16. 2011
    ..In this review, we discuss the role of Noxs in mediating oxidative stress and both pathological and physiological functions of Noxs in the heart...
  14. pmc Myocardial injection with GSK-3β-overexpressing bone marrow-derived mesenchymal stem cells attenuates cardiac dysfunction after myocardial infarction
    Jaeyeaon Cho
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Circ Res 108:478-89. 2011
    ..Glycogen synthase kinase (GSK)-3β upregulates cardiac genes in bone marrow-derived mesenchymal stem cells (MSCs) in vitro. Ex vivo modification of signaling mechanisms in MSCs may improve the efficiency of cardiac cell-based therapy (CBT)...
  15. pmc Knocking out angiotensin II in the heart
    Daniela Zablocki
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    Curr Hypertens Rep 13:129-35. 2011
    ..This review discusses current and emerging approaches towards inhibiting cardiac RAS function in order to further improve cardiovascular disease outcomes...
  16. pmc Thioredoxin 1-mediated post-translational modifications: reduction, transnitrosylation, denitrosylation, and related proteomics methodologies
    Changgong Wu
    Department of Biochemistry and Molecular Biology, UMDNJ New Jersey Medical School Cancer Center, Newark, 07103, USA
    Antioxid Redox Signal 15:2565-604. 2011
    ....
  17. pmc Endogenous muscle atrophy F-box mediates pressure overload-induced cardiac hypertrophy through regulation of nuclear factor-kappaB
    Soichiro Usui
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ, USA
    Circ Res 109:161-71. 2011
    ..Overexpression of muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, induces proteasomal degradation in cardiomyocytes. The role of endogenous MAFbx in regulating cardiac hypertrophy and failure remains unclear...
  18. ncbi Pathophysiological roles of NADPH oxidase/nox family proteins in the vascular system. -Review and perspective-
    Tetsuro Ago
    Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
    Circ J 75:1791-800. 2011
    ..This review summarizes the basis of vascular Nox proteins and discusses their pathophysiological roles in the vascular system...
  19. pmc Is reactivation of autophagy a possible therapeutic solution for obesity and metabolic syndrome?
    Sebastiano Sciarretta
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    Autophagy 8:1252-4. 2012
    ..Here we discuss the biological relevance of the dysregulation of RHEB-MTORC1 signaling and the suppression of autophagy in obesity and metabolic syndrome...
  20. pmc RASSF1A Signaling in the Heart: Novel Functions beyond Tumor Suppression
    Dominic P Del Re
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, UMDNJ New Jersey Medical School, 185 South Orange Avenue, MSB G 609, Newark, NJ 07103 2714, USA
    Mol Biol Int 2012:154283. 2012
    ..Herein, we review the role of RASSF1A in cardiac physiology and disease and highlight signaling pathways that mediate its function...
  21. pmc Pharmacological modulation of autophagy during cardiac stress
    Sebastiano Sciarretta
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    J Cardiovasc Pharmacol 60:235-41. 2012
    ..We will discuss the potential usefulness of different pharmacological activators and inhibitors of autophagy in the treatment of cardiac diseases...
  22. ncbi The importance of autophagy in cardioprotection
    Sebastiano Sciarretta
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
    High Blood Press Cardiovasc Prev 21:21-8. 2014
    ..This review will deal with the biological significance of autophagy in cardioprotection. ..
  23. pmc Elimination of NADPH oxidase activity promotes reductive stress and sensitizes the heart to ischemic injury
    Qiujun Yu
    Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA
    J Am Heart Assoc 3:e000555. 2014
    ..Here, we aimed at investigating the role of Nox in cardiac ischemic injury through gain- and loss-of-function approaches...
  24. pmc Mammalian target of rapamycin signaling in cardiac physiology and disease
    Sebastiano Sciarretta
    From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ S S, J S IRCCS Neuromed, Pozzilli, Italy S S, M V and Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University Sapienza, Rome, Italy M V
    Circ Res 114:549-64. 2014
    ..This article reviews the information available regarding the effects exerted by mTOR signaling in cardiovascular physiology and pathological states. ..
  25. pmc NOX4 regulates autophagy during energy deprivation
    Sebastiano Sciarretta
    Cardiovascular Research Institute Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark, NJ USA IRCCS Neuromed Pozzilli IS, Italy
    Autophagy 10:699-701. 2014
    ..Aside from elucidating a crucial physiological function of NOX4 during cellular energy stress, our study dissects a novel signaling mechanism that regulates autophagy under this condition. ..
  26. pmc A redox-dependent mechanism for regulation of AMPK activation by Thioredoxin1 during energy starvation
    Dan Shao
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USA
    Cell Metab 19:232-45. 2014
    ..Thus, Trx1 modulates activation of the cardioprotective AMPK pathway during ischemia, functionally linking oxidative stress and metabolism in the heart. ..
  27. pmc A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response
    Dan Shao
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey 07103, USA
    Nat Commun 5:3315. 2014
    ..These results suggest that YAP is a nuclear co-factor of FoxO1 and that the Hippo pathway negatively affects cardiomyocyte survival by inhibiting the function of YAP-FoxO1. ..
  28. pmc Muscle-specific RING finger 1 negatively regulates pathological cardiac hypertrophy through downregulation of calcineurin A
    Yasuhiro Maejima
    From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ Y M, S U, P Z, D Z, J S Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan S U, M T, S K Department of Genome Science, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, Japan M Y and Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan Y M, M I
    Circ Heart Fail 7:479-90. 2014
    ..However, how MuRF1 regulates cardiac hypertrophy and function during pressure overload (PO) remains poorly understood. We investigated the role of endogenous MuRF1 in regulating cardiac hypertrophy in response to PO in vivo...
  29. pmc Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL
    Dominic P Del Re
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
    Mol Cell 54:639-50. 2014
    ..Our findings demonstrate mitochondrial localization of Hippo signaling and identify Bcl-xL as a target that is directly modified to promote apoptosis. ..
  30. ncbi Solving the cardiac hypertrophy riddle: The angiotensin II-mechanical stress connection
    Daniela Zablocki
    From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark
    Circ Res 113:1192-5. 2013
    ....
  31. pmc Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2
    Yasuhiro Maejima
    1 Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey, USA 2 Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Med 19:1478-88. 2013
    ..These results suggest that Mst1 coordinately regulates autophagy and apoptosis by phosphorylating Beclin1 and consequently modulating a three-way interaction among Bcl-2 proteins, Beclin1 and Bax. ..
  32. pmc Activation of NADPH oxidase 4 in the endoplasmic reticulum promotes cardiomyocyte autophagy and survival during energy stress through the protein kinase RNA-activated-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcripti
    Sebastiano Sciarretta
    From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark S S, P Z, D S, D Z, N N, J S IRCCS Neuromed, Pozzilli Is, Italy S S, M V Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas L S T and Department of Clinical Molecular Medicine, School of Medicine and Psychology, Sapienza University, Rome, Italy M V
    Circ Res 113:1253-64. 2013
    ..NADPH oxidase (Nox) 4 is an enzyme that generates reactive oxygen species (ROS) at intracellular membranes. Whether Nox4 acts as a sensor of energy stress to mediate activation of autophagy is unknown...
  33. pmc Interacting with thioredoxin-1--disease or no disease?
    Tim Christian Zschauer
    Molecular Cell and Aging Research, IUF Leibniz Research Institute for Environmental Medicine, University of Duesseldorf gGmbH, Duesseldorf, Germany
    Antioxid Redox Signal 18:1053-62. 2013
    ..The interaction partners of Trx-1 differ depending on its localization in the cytosol or in the nucleus...
  34. pmc Overview of pyridine nucleotides review series
    Michinari Nakamura
    Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, 185 South Orange Ave, MSB G 609, Newark, NJ 07103, USA
    Circ Res 111:604-10. 2012
    ..This review series will highlight the functional significance of pyridine nucleotides and underscore their physiological role in cardiovascular function and their clinical relevance to cardiovascular medicine...
  35. pmc Regulation of cell survival and death by pyridine nucleotides
    Shin ichi Oka
    Cardiovascular Research Institute, UMDNJ Newark, 185 S Orange Ave, MSB G609, Newark, NJ 07103, USA
    Circ Res 111:611-27. 2012
    ..We conclude that PNs serve as an important interface for distinct cellular responses, including stress response, energy metabolism, and cell survival/death...
  36. pmc Constitutively active MEK1 rescues cardiac dysfunction caused by overexpressed GSK-3α during aging and hemodynamic pressure overload
    Yasuhiro Maejima
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry, New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Am J Physiol Heart Circ Physiol 303:H979-88. 2012
    ..In conclusion, inhibition of the MEK1/ERK pathway mediates the hypertrophy suppression and cardiac dysfunction caused by GSK-3α overexpression in cardiac myocytes...
  37. pmc Guidelines for the use and interpretation of assays for monitoring autophagy
    Daniel J Klionsky
    Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
    Autophagy 8:445-544. 2012
    ..Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field...
  38. pmc Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy
    Shouji Matsushima
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 112:651-63. 2013
    ..The cellular source of reactive oxygen species responsible for oxidation of HDAC4 remains unknown...
  39. pmc Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury
    Dominic P Del Re
    Cardiovascular Research Institute and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    J Biol Chem 288:3977-88. 2013
    ..Our findings suggest that Yap1 is critical for basal heart homeostasis and that Yap1 deficiency exacerbates injury in response to chronic MI...
  40. pmc Autophagy plays an essential role in mediating regression of hypertrophy during unloading of the heart
    Nirmala Hariharan
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    PLoS ONE 8:e51632. 2013
    ..These results suggest that autophagy and FoxO1 play an essential role in mediating regression of cardiac hypertrophy during mechanical unloading...
  41. pmc Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1α and upregulation of peroxisome proliferator-activated receptor-α
    Shouji Matsushima
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Circ Res 112:1135-49. 2013
    ..The isoform-specific contribution of Nox2 and Nox4 to ischemia/reperfusion (I/R) injury is poorly understood...
  42. ncbi Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion
    Shouji Matsushima
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Trends Cardiovasc Med 24:202-5. 2014
    ..Thus, either excessive activation or suppression of Noxs below physiological levels can induce cardiac injury. Here we discuss both detrimental and salutary functions of Nox isoforms during myocardial I/R...
  43. pmc Is autophagy in response to ischemia and reperfusion protective or detrimental for the heart?
    Sebastiano Sciarretta
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Medical Science Building G 609, Newark, NJ 07103, USA
    Pediatr Cardiol 32:275-81. 2011
    ..This review provides an overview regarding both protective and detrimental functions of autophagy in the heart and discusses possible applications of current knowledge to the treatment of heart disease...
  44. ncbi Caspase-3 mediated cleavage of MEKK1 promotes p53 transcriptional activity
    David C Zebrowski
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, 07103, USA
    J Mol Cell Cardiol 40:605-18. 2006
    ....
  45. pmc Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta 2-adrenergic receptor, but not beta 1-adrenergic receptor
    Pallavi S Peter
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA
    J Clin Invest 117:1335-43. 2007
    ....
  46. ncbi AMPK mediates autophagy during myocardial ischemia in vivo
    Hiromitsu Takagi
    Cardiovascular Research Institute, Department of Cell Biology and MolecularMedicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Autophagy 3:405-7. 2007
    ..We will discuss the role of AMPK in mediating autophagy during myocardial ischemia in vivo...
  47. ncbi The role of autophagy in mediating cell survival and death during ischemia and reperfusion in the heart
    Hiromitsu Takagi
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Antioxid Redox Signal 9:1373-81. 2007
    ..In this review, the signaling mechanism and the functional significance of autophagy during myocardial ischemia and reperfusion are discussed...
  48. ncbi Glycogen synthase kinase-3alpha reduces cardiac growth and pressure overload-induced cardiac hypertrophy by inhibition of extracellular signal-regulated kinases
    Peiyong Zhai
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA
    J Biol Chem 282:33181-91. 2007
    ..The anti-hypertrophic and pro-apoptotic effect of GSK-3alpha is mediated through inhibition of ERK...
  49. ncbi Inhibition of glycogen synthase kinase 3beta during heart failure is protective
    Shinichi Hirotani
    Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 101:1164-74. 2007
    ..Thus, downregulation of GSK-3beta during heart failure could be compensatory...
  50. pmc Endocytosis machinery is required for beta1-adrenergic receptor-induced hypertrophy in neonatal rat cardiac myocytes
    Carmine Morisco
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, 185 South Orange Avenue, MSB G 609, Newark, NJ 07103, USA
    Cardiovasc Res 78:36-44. 2008
    ..Cardiac hypertrophy by activation of the beta-adrenergic receptor (beta AR) is mediated more efficiently by the beta1-AR than by the beta2-AR. We investigated the signalling mechanism by which the beta1-AR mediates cardiac hypertrophy...
  51. ncbi Sirt1 protects the heart from aging and stress
    Chiao Po Hsu
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Biol Chem 389:221-31. 2008
    ..We propose that activation of known longevity mechanisms in the heart may represent a novel cardioprotection strategy against aging and certain types of cardiac stress, such as oxidative stress...
  52. pmc Molecular mechanisms and physiological significance of autophagy during myocardial ischemia and reperfusion
    Yutaka Matsui
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Autophagy 4:409-15. 2008
    ..In this review we discuss the functional significance of autophagy and the underlying signaling mechanism in the heart during ischemia/reperfusion...
  53. pmc Lats2 is a negative regulator of myocyte size in the heart
    Yutaka Matsui
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 103:1309-18. 2008
    ..In conclusion, Lats2 affects both growth and death of cardiac myocytes, but it primarily regulates the size of the heart and acts as an endogenous negative regulator of cardiac hypertrophy...
  54. ncbi Sirt1 regulates aging and resistance to oxidative stress in the heart
    Ralph R Alcendor
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 100:1512-21. 2007
    ..These results suggest that Sirt1 could retard aging and confer stress resistance to the heart in vivo, but these beneficial effects can be observed only at low to moderate doses (up to 7.5-fold) of Sirt1...
  55. ncbi Thioredoxin1 as a negative regulator of cardiac hypertrophy
    Tetsuro Ago
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Antioxid Redox Signal 9:679-87. 2007
    ..This review will discuss the molecular mechanisms by which Trx1 exerts antihypertrophic effects in the heart...
  56. ncbi Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction
    Mari Odashima
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Circ Res 100:1344-52. 2007
    ..Inhibition of Mst1 improves cardiac function without attenuating cardiac hypertrophy. Thus, Mst1 may be an important target of heart failure treatment...
  57. ncbi Overexpressed cardiac Gsalpha in rabbits
    Takao Nishizawa
    Cardiovascular Research Institute and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, and Children s Hospital Medical Center, Cincinnati, OH, USA
    J Mol Cell Cardiol 41:44-50. 2006
    ..Although both TG mice and rabbits with overexpressed cardiac Gsalpha exhibited enhanced heart rate and contractility, the TG rabbit does not develop cardiomyopathy, potentially due to a compensatory increase in Gialpha...
  58. ncbi Global changes in gene expression during cardiac hypertrophy: a new direction of cardiac signaling research
    Soichiro Usui
    J Mol Cell Cardiol 41:219-22. 2006
  59. ncbi An angiotensin II type 1 receptor mutant lacking epidermal growth factor receptor transactivation does not induce angiotensin II-mediated cardiac hypertrophy
    Peiyong Zhai
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA
    Circ Res 99:528-36. 2006
    ..The YIPP motif in the AT(1)R plays an important role in mediating cardiac hypertrophy in vivo...
  60. ncbi Redox regulation of growth and death in cardiac myocytes
    Junichi Sadoshima
    Antioxid Redox Signal 8:1621-4. 2006
  61. ncbi Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, 07103, USA
    Antioxid Redox Signal 8:1635-50. 2006
    ..These results suggest that, in cardiac myocytes, Trx1 upregulates mitochondrial proteins and enhances mitochondrial functions, possibly through PGC-1alpha and NRFs...
  62. pmc Thioredoxin and ventricular remodeling
    Tetsuro Ago
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Medical Science Building G 609, Newark, NJ 07103, USA
    J Mol Cell Cardiol 41:762-73. 2006
    ..In this review, we will summarize the cardiac effects of thioredoxin and the mechanisms by which thioredoxin mediates inhibition of ventricular remodeling...
  63. ncbi Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy
    Christophe Depre
    Department of Cell Biology and Molecular Medicine, UMDNJ, Newark, NJ 07103, USA
    Circulation 114:1821-8. 2006
    ....
  64. ncbi Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gsalpha
    Takao Nishizawa
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Ave, MSB G609, Newark, NJ 07103, USA
    Am J Physiol Heart Circ Physiol 292:H971-5. 2007
    ..The impaired reflex control was generalized, not only affecting the high-pressure arterial baroreflex but also the low-pressure Bezold-Jarisch reflex and the nasopharyngeal reflex...
  65. ncbi Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy
    Yutaka Matsui
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 100:914-22. 2007
    ..Furthermore, autophagy plays distinct roles during ischemia and reperfusion: autophagy may be protective during ischemia, whereas it may be detrimental during reperfusion...
  66. pmc Overcoming an energy crisis?: an adaptive role of glycogen synthase kinase-3 inhibition in ischemia/reperfusion
    Peiyong Zhai
    Circ Res 103:910-3. 2008
  67. pmc Distinct roles of GSK-3alpha and GSK-3beta phosphorylation in the heart under pressure overload
    Takahisa Matsuda
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Proc Natl Acad Sci U S A 105:20900-5. 2008
    ....
  68. ncbi The role of redox modulation of class II histone deacetylases in mediating pathological cardiac hypertrophy
    Shin ichi Oka
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    J Mol Med (Berl) 87:785-91. 2009
    ..In this review, we discuss the role of posttranslational modification of class II HDACs in mediating cardiac hypertrophy and the molecular mechanism by which Trx1 inhibits pathological cardiac hypertrophy...
  69. pmc Redox regulatory mechanism of transnitrosylation by thioredoxin
    Changgong Wu
    Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey New Jersey Medical School Cancer Center, Newark, New Jersey 07103, USA
    Mol Cell Proteomics 9:2262-75. 2010
    ....
  70. pmc NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart
    Junya Kuroda
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Proc Natl Acad Sci U S A 107:15565-70. 2010
    ..These results suggest that Nox4 in cardiac myocytes is a major source of mitochondrial oxidative stress, thereby mediating mitochondrial and cardiac dysfunction during PO...
  71. pmc Oxidative stress stimulates autophagic flux during ischemia/reperfusion
    Nirmala Hariharan
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, New Jersey, USA
    Antioxid Redox Signal 14:2179-90. 2011
    ..These results suggest that oxidative stress plays an important role in mediating autophagy during I/R, and that activation of autophagy through oxidative stress mediates myocardial injury in response to I/R in the mouse heart...
  72. pmc Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against pressure overload in mice
    Dominic P Del Re
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103 2714, USA
    J Clin Invest 120:3555-67. 2010
    ....
  73. pmc Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes
    Nirmala Hariharan
    University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Department of Cell Biology and Molecular Medicine, Newark, USA
    Circ Res 107:1470-82. 2010
    ..autophagy, a bulk degradation process of cytosolic proteins and organelles, is protective during nutrient starvation in cardiomyocytes (CMs). However, the underlying signaling mechanism mediating autophagy is not well understood...
  74. pmc Application of recombinant thioredoxin1 for treatment of heart disease
    Shouji Matsushima
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, Newark, NJ 07103, USA
    J Mol Cell Cardiol 51:570-3. 2011
    ..In this brief review, the potential of Trx1 therapy for heart disease is discussed. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."..
  75. pmc Hypotonic swelling-induced activation of PKN1 mediates cell survival in cardiac myocytes
    Katsuya Kajimoto
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Am J Physiol Heart Circ Physiol 300:H191-200. 2011
    ..These results suggest that a signaling cascade, consisting of Src, RhoA, PKN1, and ERK, is activated by HS, thereby promoting cardiac myocyte survival...
  76. pmc Silent information regulator 1 protects the heart from ischemia/reperfusion
    Chiao Po Hsu
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark, 07103, USA
    Circulation 122:2170-82. 2010
    ..Silent information regulator 1 (Sirt1), a class III histone deacetylase, retards aging and protects the heart from oxidative stress. We here examined whether Sirt1 is protective against myocardial ischemia/reperfusion (I/R)...
  77. pmc Activation of PKN mediates survival of cardiac myocytes in the heart during ischemia/reperfusion
    Hiromitsu Takagi
    Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 S Orange Avenue, Newark, NJ 07103, USA
    Circ Res 107:642-9. 2010
    ..The function of PKN, a stress-activated protein kinase, in the heart is poorly understood...
  78. pmc Nifedipine inhibits cardiac hypertrophy and left ventricular dysfunction in response to pressure overload
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, MSB G 609, Newark, NJ 07103, USA
    J Cardiovasc Transl Res 3:304-13. 2010
    ..These results suggest that a subpressor dose of nifedipine inhibits pathological hypertrophy in the heart by inhibiting activation of CaMKII and NFAT, a signaling mechanism commonly activated in pathological hypertrophy...
  79. pmc NADPH oxidase and cardiac failure
    Junya Kuroda
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, 185 S Orange Ave, MSB G609, Newark, NJ 07103, USA
    J Cardiovasc Transl Res 3:314-20. 2010
    ..In this review, the importance of NADPH oxidases as sources of increased oxidative stress in the failing heart and the role of Nox4 in mediating growth and death of cardiac myocytes are discussed...
  80. pmc Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes
    Chiao Po Hsu
    Cardiovascular Research Institute, UMDNJ Newark, 185 S Orange Ave, MSB G609, Newark, NJ 07103, USA
    Circ Res 105:481-91. 2009
    ..The cellular NAD+ synthesis is regulated by both the de novo and the salvage pathways. Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the salvage pathway...
  81. pmc Genetic inhibition of calcineurin induces diastolic dysfunction in mice with chronic pressure overload
    Ricardo J Gelpi
    Cardiovascular Research Institute and the Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
    Am J Physiol Heart Circ Physiol 297:H1814-9. 2009
    ..Thus genetic calcineurin inhibition reveals a new mechanism regulating LV diastolic function...
  82. ncbi Nicotinamide phosphoribosyltransferase regulates cell survival through autophagy in cardiomyocytes
    Chiao Po Hsu
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, New Jersey, USA
    Autophagy 5:1229-31. 2009
    ..Here we discuss the role of Nampt in regulating autophagy and potential mechanisms by which NAD(+) regulates autophagy in the heart...
  83. pmc Distinct roles of glycogen synthase kinase (GSK)-3alpha and GSK-3beta in mediating cardiomyocyte differentiation in murine bone marrow-derived mesenchymal stem cells
    Jaeyeaon Cho
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA
    J Biol Chem 284:36647-58. 2009
    ..GSK-3beta in the cytosol induces CM differentiation of MSCs through down-regulation of beta-catenin. In contrast, GSK-3alpha in the nucleus inhibits CM differentiation through down-regulation of c-Jun...
  84. pmc Bone marrow-derived cells contribute to fibrosis in the chronically failing heart
    Po Yin Chu
    Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Central, Melbourne, VIC 8008, Australia
    Am J Pathol 176:1735-42. 2010
    ..05). Taken together, our data suggest that recruitment of bone marrow-derived cells under the influence of factors, including SDF-1, may play an important role in the pathogenesis of cardiac fibrosis in heart failure...
  85. pmc Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Newark, NJ 07103, USA
    Circ Res 106:1253-64. 2010
    ..NADPH oxidases are a major source of superoxide (O(2)(-)) in the cardiovascular system. The function of Nox4, a member of the Nox family of NADPH oxidases, in the heart is poorly understood...
  86. pmc The one-two punch: knocking out angiotensin II in the heart
    Daniela Zablocki
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    J Clin Invest 120:1028-31. 2010
    ..In this issue of the JCI, Wei et al. show that ACE inhibition induces an increase in chymase activity in cardiac interstitial fluid, providing an alternate pathway for Ang II generation...
  87. pmc Injection of wild type embryonic stem cells into Mst1 transgenic blastocysts prevents adult-onset cardiomyopathy
    Qingshi Zhao
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, Newark, NJ, USA
    Stem Cell Rev 7:326-30. 2011
    ..The results expand the therapeutic capability of the ESCs to mouse models that overproduce detrimental proteins...

Research Grants30

  1. CHRONIC ADAPTATIONS TO MYOCARDIAL ISCHEMIA
    John M Canty; Fiscal Year: 2013
    ..The results will identify the stem cell and pathological sub- strate most likely to benefit patients with asymptomatic LVSD before clinical heart failure develops. ..
  2. The Center for Native and Pacific Health Disparities Research
    MARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013
    ..5) To prepare and empower our diverse Native and Pacific People communities to take ownership of their own health and wellness. ..
  3. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  4. Connexin Distribution in Physiological Versus Pathological Cardiac Hypertrophy
    Michael R Zile; Fiscal Year: 2013
    ..pathological hypertrophy, with ex- tensively characterized cytoskeletal properties in each setting. ..
  5. FAK signaling in cardiac growth and hypertrophy
    Joan M Taylor; Fiscal Year: 2013
    ..Furthermore, these cells lose the ability to divide shortly after birth, thus any damage to the heart can cause irreversible loss of function. ..
  6. Integrative Analysis of Longitudinal Studies of Aging
    Andrea M Piccinin; Fiscal Year: 2013
    ..abstract_text> ..
  7. Mechanisms of Atherogenesis in Insulin Resistance
    IRA A TABAS; Fiscal Year: 2013
    ..End of Abstract) ..
  8. Activation of sirtuins to prevent adverse cardiac remodeling after CABG
    Mahesh P Gupta; Fiscal Year: 2013
    ....