Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hypercholesterolemia: differential effects of plasma lipoproteins on monocyte function

Monocytes are recruited from the circulation into the subendothelial space where they differentiate into mature macrophages and internalize modified l ipoproteins to become lipid-laden foam cells, The accumulation of monocytes is mediated by the interaction of locally produced chemoattractant protein -1 (MCP-I) dth its receptor CCR2, The objective of the present study is to demonstrate the differential effects of plasma lipoproteins on monocyte CCR 2 expression. The CCR2 expression nas increased about 2.4-fold in monocytes isolated from hypercholesterolemic patients, compared to monocytes from no rmal controls. There was a significant correlation between CCR2 expression and plasma low density lipoprotein (LDL), Elevated levels of high density l ipoprotein (HDL) blunted and even reverted the effects of LDL on CCR2 expre ssion, both in vivo and in vitro. The causal relationship between plasma li poproteins and CCR2 expression tvas further confirmed by modulating the lip oprotein profile, Estrogen supplement therapy decreased plasma LDL choleste rol, increased plasma HDL cholesterol, and reduced CCR2 expression in hyper cholesterolemic postmenopausal women, but had no effect on the plasma lipid profile or CCR2 expression in normocholesterolemic subjects. The physiolog ical significance of altered CCR2 expression was tested by chemotaxis assay , and our results demonstrated that treatment of THP-I monocytes with LDL i nduced CCR2 expression and substantially enhanced the chemotaxis elicited b y MCP-1 j/r Our findings suggest that plasma lipoproteins differentially co ntrol monocyte function and that monocytes from hypercholesterolemic subjec ts are hyperresponsive to chemotactic stimuli, This may increase their accu mulation in the vessel wall and accelerate the pathogenic events of atherog enesis.-Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hyperchoesterolemia: differential effects of plasma lipopro teins on monocyte function.