Reverse cholesterol transport in diabetes mellitus

There are epidemiological data and experimental animal models relating the development of premature atherosclerosis with defects of the reverse choles terol transport (RCT) system. In this regard, the plasma concentrations of the high density lipoprotein (HDL) subfractions, of cholesteryl ester trans fer protein (CETP), as well as the activity of the enzyme lecithin-choleste rol acyl transferase (LCAT) play critical roles. However, there has been pl enty of evidence that atherosclerosis in diabetes mellitus (DM) is ascribed to a greater arterial wall cell uptake of modified apoB-containing lipopro teins whereas a primary or predominant defect of the RCT system is still a subject of debate. In other words, in spite of the fact that in DM the comp osition and rates of metabolism of the HDL particles are greatly altered an d display a diminished in vitro efficiency to remove cell cholesterol, defi nitive in vivo demonstration of the importance of this fact in atherogenesi s is lacking. Furthermore, the roles played by LCAT and CETP in RCT in DM a re difficult to interpret because the in vitro procedures of measurement ut ilized have either been inadequate, or inappropriately interpreted. Knock-o ut or transgenic mice are much needed models to investigate the roles of LC AT, CETP, phospholipid transfer protein (PLTP), and of a CETP inhibitor in the development of atherosclerosis of experimental DM.