Malondialdehyde-modified high-density lipoprotein cholesterol: plasma removal, tissue distribution and biliary sterol...

Evidence has been accumulating for the putative role of chemically or oxidatively altered lipoproteins in accelerating events in the atherogenic process. In this study, the movement of free cholesterol from native high density lipoprotein (HDL) and malondialdehyde (MDA)-modified HDL to the liver for biliary cholesterol secretion and bile acid transformation was examined in vivo. To this end, HDL from normal donor rats was isolated, conjugated with MDA, labelled with [14C]cholesterol and injected i.v. into rats with bile diversion. While the 6 h collection revealed no substantial differences in bile flow, less 14C excretion was recovered in the fresh bile of animals receiving MDA-modified HDL. Bile analysis indicated that a significant decline in labelled bile acid secretion characterized these rats. Compared with controls, MDA-modified HDL also caused an enhanced accumulation of [14C]cholesterol in the liver and the kidneys, with reduced delivery to the sites of steroidogenesis, i.e., the adrenals and testes. No plasma removal differences were noted in the HDL of both groups of rats. Thus, modification of HDL by MDA seems to impair the tissue distribution of its cholesterol moiety, particularly in the liver, where it accumulates at the expense of bile acid transformation.