Diabetic state induces lipid loading and altered expression and secretion of lipoprotein lipase in human monocyte-derived macrophages

Non-insulin-dependent diabetes mellitus (NIDDM) is frequently associated wi th macroangiopathies and coronary heart diseases. Lipoprotein lipase (LPL), an enzyme known to undergo significant functional alterations in diabetic state, is also a potential atherogenic protein. Since, to the best of our k nowledge, there are no data concerning LPL secreted by macrophages of NIDDM patients we conducted a study to assess the expression and activity of LPL secreted by monocyte-derived macrophages from NIDDM patients with cardiova scular complications versus cardiovascular patients without diabetes (contr ols). Isolated cells from NIDDM patients, after 7 days in culture in the pr esence of 20% autologous serum, readily exhibit a foam cell phenotype, in c ontrast to the cells from controls. Macrophages were mainly loaded with tri glycerides, whose cellular amount was well correlated to triglyceridemia of NIDDM subjects. Concomitantly, macrophages from NIDDM patients displayed a similar to six-fold decrease of mRNA expression and a similar to two-fold reduction of the activity of secreted LPL, as compared to control cells. Th ese data suggest that in complicated diabetic state, macrophage loading lea ding to foam cell formation is accelerated, at least in part, due to a dimi nished expression and activity of LPL. These observations add and extend th e data that may explain the occurrence of accelerated atherogenesis and of the atherosclerotic complications associated with diabetes. (C) 2000 Elsevi er Science Ireland Ltd. All rights reserved.