Reverse cholesterol transport in diabetes mellitus

Abstract

There are epidemiological data and experimental animal models relating the development of premature atherosclerosis with defects of the reverse cholesterol transport (RCT) system. In this regard, the plasma concentrations of the high density lipoprotein (HDL) subfractions, of cholesteryl ester transfer protein (CETP), as well as the activity of the enzyme lecithin-cholesterol acyl transferase (LCAT) play critical roles. However, there has been plenty of evidence that atherosclerosis in diabetes mellitus (DM) is ascribed to a greater arterial wall cell uptake of modified apoB-containing lipoproteins 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 composition and rates of metabolism of the HDL particles are greatly altered and display a diminished in vitro efficiency to remove cell cholesterol, definitive in vivo demonstration of the importance of this fact in atherogenesis is lacking. Furthermore, the roles played by LCAT and CETP in RCT in DM are difficult to interpret because the in vitro procedures of measurement utilized have either been inadequate, or inappropriately interpreted. Knock-out or transgenic mice are much needed models to investigate the roles of LCAT, CETP, phospholipid transfer protein (PLTP), and of a CETP inhibitor in the development of atherosclerosis of experimental DM.

Oxidized high-density lipoprotein is associated with increased plasma glucose in non-diabetic dyslipidemic subjects

“…Qualitative modifications of HDL are well described with glucose exposure [40]. For instance, a direct association has been observed between the PG level and apoA-I glycation [41,42], and this modification of HDL promotes atherosclerotic processes that are often accompanied with oxidative stress [43–45]. In addition, HDL particles from diabetic subjects have a significant reduction in their antioxidative properties, which further implicates a role of glucose in HDL oxidation [46].…”

Change of ATP binding cassette transporter A1 and liver X receptor α expression in diabetic minipig skeletal muscle Change of LXRα/ABCA1 pathway in diabetic skeletal muscle

“…In diabetic patients, the plasma lipid and lipoprotein parameters, along with the activities of lipolytic enzymes and lipid transfer proteins, are quite different from those in nondiabetic individuals [3]. In addition to the possible effects of diabetes per se, the contribution of altered gene expression of these proteins has not been fully explored.…”

Serum lecithin:cholesterol acyltransferase activity, HDL2 and HDL3 composition in hypertensive mothers and their small for gestational age newborns

“…Our data clearly show that HDL particles were qualitatively abnormal in hypertensive mothers. Alterations in HDL composition are associated with abnormal reverse cholesterol transport [26] and might contribute to the state of accelerated atherogenesis in hypertension. Previous studies have shown that the class B scavenger receptors type I (SR-BI) play important roles in the cholesterol efflux in cells [10,33].…”