Atherosclerosis is the leading cause of morbidity and mortality in the Western society. High density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol are good epidemiological predictors of risk for clinical events caused by coronary artery disease. Based on a number of recent studies in both animal models and human samples it is clear that the anti- or pro-inflammatory nature of HDL function and not HDL cholesterol levels is a sensitive indicator of the presence or absence of atherosclerosis. Hypothesis: We hypothesize that specific proteins associated with HDL are the functional determinants of its inflammatory properties and identification of such proteins will result in the development of i) novel biomarkers for the early detection of atherosclerosis, ii) biomarkers for following the efficacy of therapeutic approaches that are based on HDL function, and iii) new strategies for therapeutic interventions of atherosclerosis. Our laboratory utilizes ProteinChip technology coupled with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to facilitate protein profiling. We have successfully utilized the technology and were the first to report the identification of three panels of biomarkers for the early detection of ovarian cancer. In preliminary serum protein profiling studies using SELDI-TOF-MS, we identified an eight-protein core signature (represented by their m/z peaks) that can be used as a serum biomarker panel for identifying pro-inflammatory HDL in mice. We further demonstrated that Hemoglobin-alpha, Hemoglobin-beta, and group XII PLA2 represent three of the peaks in the eight-protein core signature. In this grant proposal, we propose to i) identify and characterize the remaining five proteins that distinguish pro-inflammatory HDL from anti-inflammatory HDL, ii) determine the biological basis for the differences in Hemoglobin and group XII PLA2, between pro-inflammatory and anti-inflammatory HDL, and iii) determine the utility and function of the new biomarkers in apoA1 mimetic peptide based therapy in mouse models of atherosclerosis. Atherosclerosis is an underlying cause for onset of cardiovascular diseases. The knowledge of protein profiles that distinguish pro-inflammatory HDL from anti-inflammatory HDL will provide will provide new strategies for early detection as well as therapeutic intervention of atherosclerosis.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Atherosclerosis and Inflammation of the Cardiovascular System Study Section (AICS)
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Liu, Lijuan
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University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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Charles-Schoeman, C; Gugiu, G B; Ge, H et al. (2018) Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis. Atherosclerosis 275:107-114
Mehta, Niyati U; Grijalva, Victor; Hama, Susan et al. (2016) Apolipoprotein E-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function. Arterioscler Thromb Vasc Biol 36:1152-63
Mehta, Niyati U; Reddy, Srinivasa T (2015) Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases. Curr Opin Lipidol 26:384-7
Morgantini, C; Meriwether, D; Baldi, S et al. (2014) HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease. Nutr Metab Cardiovasc Dis 24:594-9
Kelesidis, Theodoros; Roberts, Christian K; Huynh, Diana et al. (2014) A high throughput biochemical fluorometric method for measuring lipid peroxidation in HDL. PLoS One 9:e111716
Reddy, Srinivasa T; Navab, Mohamad; Anantharamaiah, Gattadahalli M et al. (2014) Apolipoprotein A-I mimetics. Curr Opin Lipidol 25:304-8
Gao, Feng; Liang, Bin; Reddy, Srinivasa T et al. (2014) Role of inflammation-associated microenvironment in tumorigenesis and metastasis. Curr Cancer Drug Targets 14:30-45
Charles-Schoeman, Christina; Lee, Yuen Yin; Shahbazian, Ani et al. (2013) Association of paraoxonase 1 gene polymorphism and enzyme activity with carotid plaque in rheumatoid arthritis. Arthritis Rheum 65:2765-72
Watanabe, Junji; Charles-Schoeman, Christina; Miao, Yunan et al. (2012) Proteomic profiling following immunoaffinity capture of high-density lipoprotein: association of acute-phase proteins and complement factors with proinflammatory high-density lipoprotein in rheumatoid arthritis. Arthritis Rheum 64:1828-37
Su, Feng; Grijalva, Victor; Navab, Kaveh et al. (2012) HDL mimetics inhibit tumor development in both induced and spontaneous mouse models of colon cancer. Mol Cancer Ther 11:1311-9

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