Elevated plasma cholesterol is a major risk factor for the development of atherosclerosis. Lecithin-cholesterol acyltransferase (LCAT;EC2.3.1.43). The enzyme catalyzing the esterification of free cholesterol in plasma, is believed to play an important role in the reverse cholesterol transport pathway. At present, little is known about regulation of the expression (mRNA) levels, synthesis and secretion) of the LCAT gene. The aim of the proposed study is to determine if LCAT gene expression is regulated by factors (diet and hormones) that also regulate the synthesis and secretion of apoA-I. Transcriptional regulation of LCAT gene expression will be determined by measuring hepatic mRNA levels i: a) rats challenged with diets consisting of varying amounts of saturated fatty acids, monounsaturated fatty acids, and fish oils; b) rats treated with hormones (thyroxin, triamcinolone) known to affect VLDL(apoB) and HDL)apoA-I) synthesis and secretion, c) fasted rats (72 hr), and for post- transcriptional regulation, d) cultured hepatocytes from treatments (a), (b) and (c) to measure rates of LCAT synthesis and secretion. It is expected that these treatments will produce specific changes that will influence both LCAT and apoA-I synthesis and secretion. We will determine whether changes in LCAT secretion are a (i) reflection of changes in LCAT mRNA levels and whether similar changes are seen in apoA-I and apoB mRNA levels or (ii) changes at a post-transcriptional locus. We also propose to examine the potential relationship between LCAT and apoB (triglyceride) secretion.
NIH ExPorter
NIH ExPorter