The class B, type I scavenger receptor, SR-BI, binds high density lipoprotein (HDL) and can mediate selective uptake of HDL cholesteryl esters by cultured cells. The high levels of expression of SR-BI in steroidogenic tissues and the importance of selective uptake from HDL as a source of cholesterol for steroidogenesis raised the possibility that SR-BI may participate in cholesterol delivery to steroidogenic tissues in vivo. We have used immunoblotting and immunohistochemical methods to show that SR-BI is specifically expressed in a distinctive pattern on the surfaces of steroid-producing cells in the murine adrenal gland's cortex and that its expression in vivo is induced by adrenocorticotropic hormone and suppressed by glucocorticoids. Thus, expression of SR-BI protein is coordinately regulated with adrenal steroidogenesis. These data provide strong support for the hypothesis that SR-BI is a physiologically relevant HDL receptor that provides substrate cholesterol for steroid hormone synthesis.The intercellular transport of lipids, including cholesteryl esters and triglycerides, through the blood involves their packaging into water-soluble lipoproteins and the targeted delivery of lipoprotein lipids to cells via receptor-mediated processes (1). The best understood of the lipoprotein transport systems is the LDL 1 receptor pathway of receptor-mediated endocytosis. LDL binds to its surface receptor, is internalized via coated pits, and the entire lipoprotein particle is subsequently degraded in lysosomes to release free cholesterol to the cell. HDL also delivers cholesterol to cells through a less well defined process called selective cholesterol uptake (2-12). HDL particles bind to surface receptors on target cells, their cholesteryl esters are selectively transferred into the cells without the degradation of the lipoprotein particle, and the lipid-depleted particles including their two major apolipoproteins, apoA-I and apoA-II, are released from the cells, a process that is fundamentally different from the endocytic uptake of lipoproteins mediated by members of the LDL receptor family.The HDL-cholesteryl ester selective uptake pathway occurs in cultured hepatocytes and in the liver (3, 4, 7-9, 11, 12), where it may contribute to the clearance of plasma cholesteryl ester in the terminal stage of reverse cholesterol transport (13,14). The HDL selective uptake pathway plays a prominent role in cholesterol delivery to steroidogenic cells of mice and rats where it appears to be responsible for the overwhelming majority of the uptake of HDL cholesterol (3,4,6,8,12). Indeed, HDL is significantly more effective than LDL in supplying cholesterol for cholesteryl ester accumulation and corticosterone production in adrenal glands of rats and mice (5,(15)(16)(17). Using gene knockout mice, Plump et al. (18) showed that apoA-I deficiency caused an almost complete failure to accumulate cholesteryl ester in steroidogenic cells of the adrenal gland, ovary, and testis, a result illustrating the importance of HDL-apoA-I, presum...
Background-C-reactive protein (CRP), an acute-phase reactant long considered merely an innocent bystander in the inflammatory process, is now recognized as a powerful predictor of cardiovascular events. Emerging in vitro evidence suggests that CRP may have direct proinflammatory and prothrombotic effects on monocytes and endothelial cells. To determine whether CRP directly modulates vascular cell function in vivo, we subjected wild-type mice, which do not express CRP, and human CRP-transgenic (CRPtg) mice to 2 models of arterial injury.
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