Atherosclerosis remains a major cause of mortality in the US. Even a more striking statistic is subjects with Type 2 diabetes are 4 to 5 times more likely to suffer a heart attack than someone without diabetes. Although much has been learned about the vascular cell components that contribute to atherosclerosis, it has only recently become accepted that immune cells play an important role in atherosclerosis. The mechanisms for how immune cells modulate atherosclerosis are unclear, and this is an emerging field of research that could lead to promising new therapies. We are a long-standing team of investigators who have been studying atherosclerosis and type 2 diabetes for the last 15 years. The focus of this PPG renewal is to study the immunobiology of atherosclerosis. Project 1 will study T regulatory lymphocyte function in atherosclerosis. Project 2 will investigate the synergy between endotoxemia and oxidized cholesteryl esters in TLR-mediated vascular inflammation. Project 3 will test the role of the transcriptional repressor ld3 in modulating B lymphocyte function in atherosclerosis. A Human Phenotyping and Immune Cell Core will provide human blood samples for immune cell phenotyping for each project. The purpose of this Administrative Core (Core A) is to coordinate the PPG by providing scientific administration, grant and fiscal management, and coordination of scientific advisory meetings.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL055798-16A1
Application #
8396698
Study Section
Special Emphasis Panel (ZHL1-CSR-A (M1))
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
16
Fiscal Year
2012
Total Cost
$130,671
Indirect Cost
$55,573
Name
La Jolla Institute
Department
Type
DUNS #
603880287
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Jeong, Se-Jin; Kim, Sinai; Park, Jong-Gil et al. (2018) Prdx1 (peroxiredoxin 1) deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux. Autophagy 14:120-133
Gao, Chuan; Tabb, Keri L; Dimitrov, Latchezar M et al. (2018) Exome Sequencing Identifies Genetic Variants Associated with Circulating Lipid Levels in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study (IRASFS). Sci Rep 8:5603
Gaddis, Dalia E; Padgett, Lindsey E; Wu, Runpei et al. (2018) Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis. Nat Commun 9:1095
Que, Xuchu; Hung, Ming-Yow; Yeang, Calvin et al. (2018) Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature 558:301-306
Senders, Max L; Que, Xuchu; Cho, Young Seok et al. (2018) PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody Detects Clinically Relevant Atherothrombosis. J Am Coll Cardiol 71:321-335
Capoulade, Romain; Chan, Kwan L; Mathieu, Patrick et al. (2017) Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial. Atherosclerosis 260:1-7
van Capelleveen, Julian C; Bernelot Moens, Sophie J; Yang, Xiaohong et al. (2017) Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study. Arterioscler Thromb Vasc Biol 37:1206-1212
Pechlaner, Raimund; Tsimikas, Sotirios; Yin, Xiaoke et al. (2017) Very-Low-Density Lipoprotein-Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-III. J Am Coll Cardiol 69:789-800
Lee, Sang-Rok; Prasad, Anand; Choi, Yun-Seok et al. (2017) LPA Gene, Ethnicity, and Cardiovascular Events. Circulation 135:251-263
Kamstrup, Pia R; Hung, Ming-Yow; Witztum, Joseph L et al. (2017) Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study. Arterioscler Thromb Vasc Biol 37:1570-1578

Showing the most recent 10 out of 217 publications