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 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.
Lipid Metabolism Laboratory (LIM 10), Hospital das Clínicas, The University of São Paulo Medical School, São Paulo, Brazil. lipideq@usp.br
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Quintão
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Medina
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Passarelli
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology*; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology*; D006023:Glycoproteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase