The biological basis for the sex differential in longevity in Western societies represents a phenomenon of increasing importance in our aging society and is the primary interest of this investigative team. Nearly half of this differential is attributable to the sex differential in atherosclerosis and the majority of this in turn to the sex differential in lipoprotein lipid levels, much of which can be reproduced in postmenopausal women given estrogen replacement therapy (with or without progestational agents). However, the precise mechanisms and points of regulation at which sex steroids (androgens as well as estrogens) modulate human lipoprotein metabolism have been only partially defined. Moreover, studies of the type proposed have the potential of informing research on the points of regulation of normal human lipoprotein metabolism. Hence the purpose of this proposal is to test the effects of estrogen replacement on two, related aspects of lipoprotein metabolism: 1. Reverse cholesterol transport through the """"""""lipid transfer zone"""""""", measuring cholesterol ester transfer activity and protein (CETP) and apo- lipoprotein (apo) E by immunoassay and the distribution of lipids and apo E across the IDL-LDL-HDL continuum; 2. The turnover of high density lipoprotein (HDL), its apolipoproteins and subfractions, with special reference to the activity of post-heparin triglyceride lipase (HTGL) and CETP.
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