Tobacco Documents Online

THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. 900 11IIRD AVENUE NEW YORK. N.Y. 10022 Memorandum To: Dr. J.F.Glenn and Staff From: D.H.Ford Re: Site visit with Dr. I. Goldberg, Columbia University, NYC, August 18, 1989. Grant No. 2398 entitled "Regulation of plasma high density lipoprotien (HDL) catabolism." Goals: To determine what events are responsible for variation in HDL levels in humans; to determine if alterations in HDL composition are responsible for its increased catabolism and reduced plasma levels. Dr. Goldberg introduced the discussion of his program by presenting a nice review of the relative roles of HDL, LDL,VLDL, lipoprotein lipase and triglyceride levelss as relatied to atherosclerosis and coronary heart disease. Incorporated in this discussion were the results of a recent publication on the release of endothelial call lipoprotein lipase by plasma lipoproteins and free fatty acids (JBC 264:4349-4355,1989), results from a report in press on the localization of lipoprotein lipase mRNA in slected rat tissue, including brain (specifically pyramidal cells of the hippocampus, in the cerebral cortex and intermediate pituitary lobe) as well as in the adrenal and kidney medulla (J. Lipid Research) and finally results from a report submitted for publication on the role of-lipoprotein lipase in the regulation of HDL catabolism in normal and lipase inhibited monkeys (cynomologus). His last report utilizing a monkey model to study variations in HDL in humans suggests that variations in HDL level are due to variations in the rate of HDL catabolism which may be a consequence of differences in LPL activity and in the rates of triglyceride-rich lipoprotein lipolysis. He notes that interventions which increase LPL activity (chronic exercise, insulin treatment of diabetes mellitus, or treatment with fibric acids) would be expected to reduce plasma triglyceride levels and increase HDL levels. The remnants of some triglyceride- rich lipoproteins appear to atherogenic and when taken up by macro- phages convert them into foam cells. Further, since postprandial lipoproteins remain in circulation longer if lipoprotein lipase is inhibited, this could increase the risk for atherosclerosis. Thus, he concludes that atherogenic risk as measured by HDL levles and by interventions which decrease risk may be both due to variations in the activity of the lipoprotein lipase enzyme. Dr. Goldberg further noted that the levles of HDL in the blood may not accurately reflect the level of activity of this enzyme. The results of Dr. Goldberg's investigation appear relevent to the interests of CTR in cardiovascular disease and appear likely to further define factors which influence the likelihood of developing atherosclerosis. DHF