Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Oxidative Stress and Inflammation play a pivotal role in atherogenesis. CANDIDATE: In the funded K24 Award (Year 4), the principal investigator has made excellent progress with respect to productivity (publications and procuring grants), mentoring and enhancing his research program. RESEARCH PLAN: In the present proposal, which aims to further strengthen his research program and mentoring in patient-oriented research, the principal investigator proposes the following studies: 1) The Effect of High dose Alpha tocopherol Supplementation on Oxidative Stress (OS), Inflammation and Carotid Atherosclerosis in Patients with Coronary artery disease ; 2) Monocyte Function and Inflammation in Type 1 Diabetes and its Modulation with Simvastatin therapy; 3) The Effect of Simvastatin Therapy on Monocytic Inflammatory Markers and hsCRP Levels in Patients with the Metabolic Syndrome; 4) A Dose-Response Effect of Lycopene supplementation on Biomarkers of OS; 5) Effect of Alpha tocopherol and Gamma tocopherol Supplementation on Biomarkers of OS and Inflammation in Patients with the Metabolic Syndrome. Biomarkers of OS that will be analyzed include urinary F2-isoprostanes, LDL oxidative susceptibility; biomarkers of inflammation will include hs-CRP, SAA, plasma soluble cell adhesion molecules, monocyte superoxide anion release, cytokine release, adhesion to endothelium. MENTORING PLAN: These focused and cohesive clinical studies in Nutrition and Metabolism, in addition to the didactic courses and Mentored Clinical Research Training Program offered at UC-Davis will provide an excellent training ground for the junior faculty and clinical fellows in the area of patient-oriented research. Thus, studies outlined in this proposal will clearly enhance the long-term objectives of the principal investigator, since his major interest is in the area of lipoproteins, oxidative stress and inflammation in diabetes and atherosclerosis and their modulation. ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
2K24AT000596-07
Application #
6875965
Study Section
Special Emphasis Panel (ZAT1-CP (17))
Program Officer
Pearson, Nancy
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
7
Fiscal Year
2005
Total Cost
$142,733
Indirect Cost
Name
University of California Davis
Department
Pathology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Jialal, Ishwarlal; Huet, Beverley A; Kaur, Harmeet et al. (2012) Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care 35:900-4
(2012) Retraction. Alpha-lipoic acid supplementation and diabetes. Nutr Rev 70:482
Yun, Jung-Mi; Chien, Alexander; Jialal, Ishwarlal et al. (2012) Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights. J Nutr Biochem 23:699-705
Devaraj, S; Jialal, G; Cook, T et al. (2011) Low vitamin D levels in Northern American adults with the metabolic syndrome. Horm Metab Res 43:72-4
Devaraj, Sridevi; Siegel, David; Jialal, Ishwarlal (2011) Statin therapy in metabolic syndrome and hypertension post-JUPITER: what is the value of CRP? Curr Atheroscler Rep 13:31-42
Gower, R Michael; Wu, Huaizhu; Foster, Greg A et al. (2011) CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to vascular cell adhesion molecule-1. Arterioscler Thromb Vasc Biol 31:160-6
Devaraj, Sridevi; Jialal, Ishwarlal; Rockwood, Jason et al. (2011) Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity. Clin Nutr 30:668-71
Devaraj, Sridevi; Tobias, Peter; Kasinath, Balakuntalam S et al. (2011) Knockout of toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy. Arterioscler Thromb Vasc Biol 31:1796-804
Devaraj, Sridevi; Jialal, Ishwarlal (2011) C-reactive protein polarizes human macrophages to an M1 phenotype and inhibits transformation to the M2 phenotype. Arterioscler Thromb Vasc Biol 31:1397-402
Yun, Jung-Mi; Jialal, Ishwarlal; Devaraj, Sridevi (2011) Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J Nutr Biochem 22:450-8

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