Introduction Men exhibit a higher incidence of cardiovascular dis selleck kinase inhibitor eases than women, and men have lower circulating levels of antiatherogenic high density lipoprotein cholesterol. Inhibitors,Modulators,Libraries Evidence indicates that the cardiovascular actions of sex steroids are primary factors in mediating this gender related difference. Because androgen admin istration lowers HDL C levels in both genders, par ticularly at supraphysiological plasma concentrations, endogenous androgens, such as testosterone, have been implicated in influencing the lipoprotein profile and risk for cardiovascular Inhibitors,Modulators,Libraries diseases. However, the rela tionship between androgens and lipid metabolism CVD risk factors is highly complex, and the results of different studies are contradictory. A likely explanation for the complex relationship between androgens and CVD is that androgens affect many risk factors.

For example, andro gens can increase muscle mass, decrease visceral fat mass in some subjects, improve coronary blood flow, Inhibitors,Modulators,Libraries increase mood and motivation, reduce lipoprotein and leptin, improve insu lin sensitivity, and provide other potential benefits, such as anti inflammatory effects. To understand the role of endogenous and therapeutic androgens in CVD, it will be necessary to identify the mechanisms responsible for the changes in HDL C levels. Apolipoprotein M is mainly expressed by hepa tocytes and tubular epithelial cells in the kidney and is associated mainly with high density lipoprotein in human plasma. Mice deficient in ApoM are impaired in their ability to produce preB HDL.

Further, overexpres sion of ApoM in LDL receptor knockout mice protects against Inhibitors,Modulators,Libraries atherosclerosis in mice fed a cholesterol rich diet. These findings indicate that ApoM is important for preB HDL formation and may exert a protective effect on the development and progression of atherosclerosis. More over, evidence indicates that ApoM levels are possibly regulated by several cytokines in the in the human HepG2 cell line, which was derived from hepatocellular carcinoma. However, Inhibitors,Modulators,Libraries the pathophysiological importance of ApoM in humans is still unknown. The androgen receptor is expressed in the liver, the primary site of lipoprotein regulation, in which it could conceivably alter the expression of genes controlling HDL metabolism. Apolipoprotein AI levels are reduced after treatment with androgens, suggesting the decreased synthesis or increased catabolism of this core constituent of HDL particles.

ApoM, which is one of the main constituents of HDL particles, is involved in HDL metab olism and formation of preB HDL. Whether androgens regulate the secretion of apoM and further mediate lipid metabolism remains unknown. To further understand the possible effect of androgens on ApoM secretion, we investigated found the effects of 5 dihydrotestosterone on the regulation of ApoM expression by HepG2 cells.