Plasma high density lipoprotein cholesterol (HDL-C) is an important but poorly understood negative risk factor for cardiovascular disease. It is thought that HDL transfers cholesterol from peripheral tissue, such as its site of synthesis in the arterial wall, to the liver for degradation or recycling. This process, reverse cholesterol transport, has been the subject of numerous investigations. An important part of the reverse cholesterol transport pathway involves the remodeling of HDL. The broad goals of this project are to improve our understanding of how HDL particles are remodeled by the major HDL-modifying proteins, which include cholesteryl ester transfer protein (CETP), lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), and hepatic lipase (HL). These studies will investigate the role of triglyceride-rich lipoproteins and the interaction of each of the HDL-modifying proteins with model reassembled HDL (R-HDL) and native HDL subfractions with known composition, charge, and size. The following specific goals will be pursued as part of the broader topic of understanding HDL-remodeling: 1] determination of the acyl chain and molecular species specificity of CETP and PLTP by measuring the kinetics of lipid transfer from HDL and R-HDL to single bilayer vesicles in the presence and absence of purified CETP and PLTP; 2] measurement of the PLTP- and CETP-mediated rates of transfer of (3H)phosphatidylcholine from donors of native and model HDL to single bilayer vesicles as a function of surface structure and charge of the donor and acceptor; 3] quantification of the contributions of CETP, PLTP, and LCAT to the maturation of preBeta-HDL into HDL2 and HDL3; 4] comparison of the lipid and the fatty acid compositions of the phosphatidylcholines of the plasma membranes of fibroblasts with those of pre-Beta-HDL that are formed during the incubation of plasma with fibroblasts; and 5] use of purified CETP and PLTP to determine the effects of PLTP on the CETP-mediated transfer of very low density lipoprotein-triglycerides to HDL2 and HDL3. Key analytical methods involved are molecular sieve chromatography, reverse phase HPLC, gradient gel electrophoresis, and ultracentrifugation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030914-12
Application #
2717270
Study Section
Metabolism Study Section (MET)
Project Start
1983-07-01
Project End
2001-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
12
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Rosales, C; Davidson, W S; Gillard, B K et al. (2016) Speciated High-Density Lipoprotein Biogenesis and Functionality. Curr Atheroscler Rep 18:25
Rodriguez, Perla J; Gillard, Baiba K; Barosh, Rachel et al. (2016) Neo High-Density Lipoprotein Produced by the Streptococcal Serum Opacity Factor Activity against Human High-Density Lipoproteins Is Hepatically Removed via Dual Mechanisms. Biochemistry 55:5845-5853
Pownall, Henry J; Gotto Jr, Antonio M (2016) New Insights into the High-Density Lipoprotein Dilemma. Trends Endocrinol Metab 27:44-53
Pownall, Henry J; Schwartz, Anne V; Bray, George A et al. (2016) Changes in regional body composition over 8 years in a randomized lifestyle trial: The look AHEAD study. Obesity (Silver Spring) 24:1899-905
Rosales, Corina; Patel, Niket; Gillard, Baiba K et al. (2015) Apolipoprotein AI deficiency inhibits serum opacity factor activity against plasma high density lipoprotein via a stabilization mechanism. Biochemistry 54:2295-302
Pownall, Henry J; Bray, George A; Wagenknecht, Lynne E et al. (2015) Changes in body composition over 8 years in a randomized trial of a lifestyle intervention: the look AHEAD study. Obesity (Silver Spring) 23:565-72
Pownall, Henry J; Gillard, Baiba K; Gotto Jr, Antonio M (2013) Setting the course for apoAII: a port in sight? Clin Lipidol 8:551-560
Vasudevan, Madhuri; Tchoua, Urbain; Gillard, Baiba K et al. (2013) Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome. J Clin Lipidol 7:661-70
Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul et al. (2013) Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function. Arterioscler Thromb Vasc Biol 33:1714-21
Wooten, Joshua S; Nambi, Preethi; Gillard, Baiba K et al. (2013) Intensive lifestyle modification reduces Lp-PLA2 in dyslipidemic HIV/HAART patients. Med Sci Sports Exerc 45:1043-50

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