Sleep Apnea and Dysregulation of Lipid Metabolism

Summary

Principal Investigator: Vsevolod Y Polotsky
Abstract: Obstructive sleep apnea (OSA) leads to high cardiovascular mortality, which has been attributed to metabolic abnormalities induced by chronic intermittent hypoxia (IH). We have developed a mouse model of chronic IH, which mimics the oxygen profile in human OSA, and have shown that IH causes dyslipidemia, hepatic steatosis and insulin resistance. We have also shown that IH leads to metabolic dysfunction by stimulating a key hepatic enzyme of lipid biosynthesis, stearoyl Coenzyme A desaturase 1 (SCD-1). We accumulated evidence allowing to formulate our main hypothesis that chronic IH causes dyslipidemia and hepatic steatosis by up-regulating SCD-1 via two major pathways, (1) induction of hepatic hypoxia inducible factor 1 (HIF-1) with downstream activation of key factors of lipid biosynthesis, sterol regulatory element binding protein 1c (SREBP-1c), liver X receptors (LXRs) and peroxisome proliferator-activated receptor gamma (PPAR[unreadable]), (2) activation of the sympathetic nervous system (SNS) resulting in increased hepatic glucose output and up-regulation of carbohydrate response element-binding protein ChREBP. In Specific Aim #1 we will examine the role of HIF-1 in metabolic dysfunction during IH. We propose that IH up-regulates SCD-1 via HIF-1 and therefore (A) IH-induced increase in hepatic SCD-1, dyslipidemia and hepatic steatosis will be attenuated in mice with HIF-1[unreadable] deficient livers;(B) hypoxic up-regulation of SCD-1 will be abolished by HIF-1[unreadable] deficiency in isolated hepatocytes;(C) constitutive expression of HIF-1[unreadable] in mouse hepatocytes will induce SCD-1;(D) hypoxia will induce the SCD-1 promoter, this induction will be abolished by HIF-1[unreadable] deficiency, and constitutively active HIF-1[unreadable] will be sufficient to drive promoter activity. In Specific Aim #2, we will determine pathways downstream of HIF-1, by which hypoxia induce SCD-1 in cultured hepatocytes. We propose that HIF-1 up-regulates SCD-1 via increased activity of LXR, PPAR[unreadable] and SREBP-1c and therefore (A) SCD-1 up-regulation by hypoxia or by constitutive expression of HIF-1[unreadable] will be attenuated by deficiency of LXR[unreadable]/[unreadable], PPAR[unreadable] and SREBP-1c and abolished by the combined deficiency of these transcription factors, (B) induction of the SCD-1 promoter by hypoxia or by constitutive expression of HIF- 1[unreadable] will be attenuated by deficiency of LXR[unreadable]/[unreadable], PPAR[unreadable] and SREBP-1c and abolished by the combined deficiency of these transcription factors. In Specific Aim #3, we will explore the role of ChREBP in up- regulation of hepatic SCD-1 during IH. We propose that IH acts through the SNS to induce ChREBP, which up-regulates SCD-1 leading to dyslipidemia and hepatic steatosis. We hypothesize that (A) induction of hepatic ChREBP by IH will be abolished and up-regulation of SCD-1 will be attenuated by the blockade of the SNS;(B) ChREBP deficiency will attenuate chronic IH-induced increases in hepatic SCD- 1, dyslipidemia and hepatic steatosis.
Funding Period: 2005-07-01 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. ncbi Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha
    Jianguo Li
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Physiol Genomics 25:450-7. 2006
  2. pmc Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Best Pract Res Clin Endocrinol Metab 24:843-51. 2010
  3. pmc Chronic intermittent hypoxia induces lung growth in adult mice
    Christian Reinke
    Department of Medicine, Div of Pulmonary Medicine, Johns Hopkins University, Baltimore, MD, USA
    Am J Physiol Lung Cell Mol Physiol 300:L266-73. 2011
  4. pmc Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia
    Ronghua Yang
    Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Am J Physiol Heart Circ Physiol 300:H1467-76. 2011
  5. ncbi Sleep apnea determines soluble TNF-α receptor 2 response to massive weight loss
    Maria Pallayova
    Johns Hopkins Sleep Disorders Center, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    Obes Surg 21:1413-23. 2011
  6. pmc Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Eur Heart J 33:783-90. 2012
  7. pmc Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes
    Christian Reinke
    Dept of Internal Medicine, Division of Pulmonary Diseases, Univ Hospital Giessen and Marburg GmbH, 35043 Marburg, Germany
    J Appl Physiol (1985) 111:881-90. 2011
  8. ncbi Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Obesity (Silver Spring) 19:2167-74. 2011
  9. pmc Obstructive sleep apnea: an emerging risk factor for atherosclerosis
    Luciano F Drager
    Hypertension Unit, Sleep Laboratory, Pulmonary Division, Heart Institute InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil
    Chest 140:534-42. 2011
  10. pmc Effects of sleep apnea on nocturnal free fatty acids in subjects with heart failure
    Jonathan C Jun
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Sleep 34:1207-13. 2011

Detail Information

Publications36

  1. ncbi Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha
    Jianguo Li
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Physiol Genomics 25:450-7. 2006
    ....
  2. pmc Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Best Pract Res Clin Endocrinol Metab 24:843-51. 2010
    ..IH models of OSA have improved our understanding of the metabolic impact of OSA, but further studies are needed before we can translate recent basic research findings to clinical practice...
  3. pmc Chronic intermittent hypoxia induces lung growth in adult mice
    Christian Reinke
    Department of Medicine, Div of Pulmonary Medicine, Johns Hopkins University, Baltimore, MD, USA
    Am J Physiol Lung Cell Mol Physiol 300:L266-73. 2011
    ..We conclude that IH increases alveolar surface area by stimulating lung growth in adult mice...
  4. pmc Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia
    Ronghua Yang
    Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Am J Physiol Heart Circ Physiol 300:H1467-76. 2011
    ..Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH...
  5. ncbi Sleep apnea determines soluble TNF-α receptor 2 response to massive weight loss
    Maria Pallayova
    Johns Hopkins Sleep Disorders Center, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    Obes Surg 21:1413-23. 2011
    ..We sought to determine if any biomarkers can predict amelioration of sleep apnea achieved by bariatric surgery. We hypothesized that surgical WL would substantially reduce severity of sleep apnea and levels of proinflammatory cytokines...
  6. pmc Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Eur Heart J 33:783-90. 2012
    ..This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP)...
  7. pmc Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes
    Christian Reinke
    Dept of Internal Medicine, Division of Pulmonary Diseases, Univ Hospital Giessen and Marburg GmbH, 35043 Marburg, Germany
    J Appl Physiol (1985) 111:881-90. 2011
    ..IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens...
  8. ncbi Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Obesity (Silver Spring) 19:2167-74. 2011
    ..In conclusion, CIH exacerbates IR and induces steatohepatitis in DIO mice, suggesting that CIH may account for metabolic dysfunction in obesity...
  9. pmc Obstructive sleep apnea: an emerging risk factor for atherosclerosis
    Luciano F Drager
    Hypertension Unit, Sleep Laboratory, Pulmonary Division, Heart Institute InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil
    Chest 140:534-42. 2011
    ..This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area...
  10. pmc Effects of sleep apnea on nocturnal free fatty acids in subjects with heart failure
    Jonathan C Jun
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Sleep 34:1207-13. 2011
    ..The objective of this study was to determine the effect of intermittent hypoxia on FFA levels during sleep in patients with heart failure...
  11. pmc Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice
    Jonathan C Jun
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Am J Physiol Endocrinol Metab 303:E377-88. 2012
    ..We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion...
  12. pmc Metabolic consequences of high-fat diet are attenuated by suppression of HIF-1α
    Mi Kyung Shin
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 7:e46562. 2012
    ..2 mg/dl in untreated mice, p<0.01), plasma insulin, hepatic glucose output, and liver fat content. These findings demonstrate that the metabolic consequences of DIO are attenuated by HIF-1α ASO treatment...
  13. pmc Thermoneutrality modifies the impact of hypoxia on lipid metabolism
    Jonathan C Jun
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Am J Physiol Endocrinol Metab 304:E424-35. 2013
    ..Our study underscores the importance of ambient temperature for hypoxia research, especially in studies of lipid metabolism...
  14. pmc Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Am J Respir Crit Care Med 188:240-8. 2013
    ..The effects and mechanisms of Angptl4 up-regulation in sleep apnea are unknown...
  15. pmc Macrophage A2A adenosinergic receptor modulates oxygen-induced augmentation of murine lung injury
    Neil R Aggarwal
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    Am J Respir Cell Mol Biol 48:635-46. 2013
    ..ADORA2A is protective against lung injury after LPS and oxygen. Oxygen after LPS increases macrophage activation to augment lung injury by inhibiting the ADORA2A pathway...
  16. pmc Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues
    Qiaoling Yao
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    J Lipid Res 54:1058-65. 2013
    ..The antibody reversed the effects of CIH on LPL in adipose tissue and lungs. In conclusion, CIH inactivates LPL by upregulating Angptl4, but inhibition of TG uptake occurs predominantly via an Angptl4/LPL-independent mechanism...
  17. pmc Sleep disorders and the development of insulin resistance and obesity
    Omar Mesarwi
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Endocrinol Metab Clin North Am 42:617-34. 2013
    ..Obesity is a major risk factor for OSA, but whether OSA leads to obesity is unclear. The quality and quantity of sleep may profoundly affect obesity and glucose tolerance, and should be routinely assessed by clinicians. ..
  18. pmc The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome
    Luciano F Drager
    Heart Institute InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil
    PLoS ONE 5:e12065. 2010
    ..Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS...
  19. pmc Intermittent and sustained hypoxia induce a similar gene expression profile in human aortic endothelial cells
    Vsevolod Y Polotsky
    Divisions of Pulmonary and Critical Care Medicine and
    Physiol Genomics 41:306-14. 2010
    ..In conclusion, short exposures to IH and SH upregulate proinflammatory and antioxidant genes in HAEC and increase secretion of proinflammatory cytokines IL-8 and IL-6 into media in similar fashions. ..
  20. ncbi Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia
    Jianguo Li
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA
    J Appl Physiol 102:557-63. 2007
    ..In conclusion, CIH leads to hypercholesterolemia and lipid peroxidation in the absence of obesity, and the degree of metabolic dysregulation is dependent on the severity of the hypoxic stimulus...
  21. pmc Chronic intermittent hypoxia induces atherosclerosis
    Vladimir Savransky
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Am J Respir Crit Care Med 175:1290-7. 2007
    ..A causal link between obstructive sleep apnea and atherosclerosis has not been established...
  22. ncbi Chronic intermittent hypoxia predisposes to liver injury
    Vladimir Savransky
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA
    Hepatology 45:1007-13. 2007
    ..CONCLUSION: In the absence of obesity, CIH leads to mild liver injury via oxidative stress and excessive glycogen accumulation in hepatocytes and sensitizes the liver to a second insult, whereas NASH does not develop...
  23. ncbi Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia
    Jianguo Li
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Physiol Genomics 31:273-80. 2007
    ..We conclude that hyperlipidemia in response to IH is mediated via the SREBP-1 pathway. Our data suggest that the SREBP-1 pathway could be used as a therapeutic target in patients with both OSA and hyperlipidemia...
  24. ncbi Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver
    Vladimir Savransky
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Am J Physiol Gastrointest Liver Physiol 293:G871-7. 2007
    ..We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet...
  25. pmc Intermittent hypoxia has organ-specific effects on oxidative stress
    Jonathan Jun
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Am J Physiol Regul Integr Comp Physiol 295:R1274-81. 2008
    ..In p47(phox)-deficient mice, MDA levels were higher at baseline and, unexpectedly, decreased during IH. In conclusion, oxidative stress levels and pathways under IH conditions are organ and duration specific...
  26. pmc Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase
    Vladimir Savransky
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    Circ Res 103:1173-80. 2008
    ..In conclusion, CIH is associated with dyslipidemia and overexpression of hepatic SCD in both humans and mice alike; SCD-1 deficiency attenuates CIH-induced dyslipidemia and atherosclerosis in mice...
  27. pmc Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity
    Vsevolod Y Polotsky
    Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Am J Respir Crit Care Med 179:228-34. 2009
    ..Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity...
  28. pmc Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice
    Thomas E Sussan
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
    PLoS ONE 3:e3791. 2008
    ..Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis...
  29. pmc Chronic intermittent hypoxia and acetaminophen induce synergistic liver injury in mice
    Vladimir Savransky
    Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    Exp Physiol 94:228-39. 2009
    ..We conclude that CIH and chronic APAP treatment lead to synergistic liver injury, which may have clinical implications for patients with OSA...
  30. ncbi Metabolic consequences of sleep-disordered breathing
    Jonathan Jun
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    ILAR J 50:289-306. 2009
    ..Identification of OSA as a potential causative factor in MetS would have immense clinical impact and could improve the management and understanding of both disorders...
  31. ncbi Cardiovascular aspects in obstructive sleep apnea syndrome--molecular issues, hypoxia and cytokine profiles
    Lena Lavie
    Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Respiration 78:361-70. 2009
    ..In light of the new findings in the field of cytokines, their potential involvement in endothelial dysfunction and cardiovascular morbidity in OSAS is discussed...
  32. pmc Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice
    Jonathan Jun
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, United States
    Atherosclerosis 209:381-6. 2010
    ..This increased risk may be attributable to more extensive or unstable atherosclerotic plaques in subjects with OSA. We studied the effect of chronic IH in atherosclerosis-prone mice...
  33. pmc Moderate oxygen augments lipopolysaccharide-induced lung injury in mice
    Neil R Aggarwal
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
    Am J Physiol Lung Cell Mol Physiol 298:L371-81. 2010
    ..We believe these results strongly support an effect of lower concentrations of oxygen to augment the severity of a mild preexisting lung injury and warrants further investigation in both animals and humans...
  34. pmc Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis
    Luciano F Drager
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Curr Opin Endocrinol Diabetes Obes 17:161-5. 2010
    ..The aim of this review is to summarize current evidence about the impact of obstructive sleep apnea (OSA) and intermittent hypoxia on dyslipidemia and provide future perspectives in this area...
  35. ncbi New frontiers in obstructive sleep apnoea
    Najib T Ayas
    Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada
    Clin Sci (Lond) 127:209-16. 2014
    ..Finally, the section on cardiovascular biomarkers reviews the evidence supporting the use of these biomarkers to both measure some of the negative consequences of OSA, as well as the potential benefits of OSA therapies. ..

Research Grants30

  1. Hepatic Lipase, PPAR-delta and Fatty Acid Metabolism
    JONATHAN DAVID BROWN; Fiscal Year: 2013
    ..abstract_text> ..
  2. Molecular Mechanisms of Mitigation of Insulin Induction of SREBP-1c by N-3 PUFA
    Marshall B Elam; Fiscal Year: 2013
    ..Understanding how PUFA causes this will lead to more effective treatments for high triglyceride levels in individuals with obesity and type II diabetes to reduce risk of heart attack and stroke. ..
  3. CELLULAR AND MOLECULAR BIOLOGY OF LIPOPROTEIN METABOLISM
    Michael C Phillips; Fiscal Year: 2013
    ..The reasons for this protective effect are not understood fully and this project seeks to uncover the molecular mechanisms underlying the beneficial properties of HDL. ..
  4. Hepatic Steatosis and ER Stress-Inducible Transcription Factor CREBH
    Kezhong Zhang; Fiscal Year: 2013
    ..Understanding the stress-induced molecular mechanisms in hepatic lipid accumulation and its associated pathogenesis is a key prerequisite for the development of new diagnostics and therapeutics targeting NAFLD. ..
  5. A Novel Cellular Mechanism for Reducing Hyperlipidemia
    Jingwen Liu; Fiscal Year: 2013
    ....
  6. Mechanisms of Atherogenesis in Insulin Resistance
    IRA A TABAS; Fiscal Year: 2013
    ..End of Abstract) ..
  7. Hypo-Lipidemic Actions of Creosote Bush-Derived NDGA
    Salman Azhar; Fiscal Year: 2013
    ....
  8. A trial to determine the effect of psoriasis treatment on cardiometabolic disease
    Joel M Gelfand; Fiscal Year: 2013
    ..These results will be a critical step in determining how treatment of psoriasis affects CV risk in this vulnerable patient population and will concurrently improve scientific knowledge of off target effects of the commonly used TNF-I s. ..
  9. Cardiac Myosin Binding Protein-C: Structure, Function, and Regulation
    David M Warshaw; Fiscal Year: 2013
    ..abstract_text> ..
  10. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  11. Regulation of Hepatic SphK2 by Bile Acids: Effects on Lipid Metabolism
    HUIPING ROSE ZHOU; Fiscal Year: 2013
    ..Also, this study has potential impact on the identification and development of novel therapeutic targets for effective treatment of NAFLD and other related metabolic diseases. ..
  12. 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. ..