Mast Cells Promote Atherosclerosis by Inducing Both an Atherogenic Lipid Profile and Vascular Inflammation

Accumulating in vitro and in vivo studies have proposed a role for mast cells in the pathogenesis of atherosclerosis. Here, we studied the role of mast cells in lipoprotein metabolism, a key element in the atherosclerotic disease. Male mice deficient in low-density lipoprotein receptors and mast cells on a Western diet for 26 weeks had significantly less atherosclerotic changes both in aortic sinus (55%, P = 0.0009) and in aorta (31%, P=0.049), as compared to mast cell-competent littermates. Mast cell-deficient female mice had significantly less atherosclerotic changes in aortic sinus (43%, P=0.011). Furthermore, we found a significant positive correlation between the extent or atherosclerosis and the number of adventitial/perivascular mast cells in aortic sinus of mast cell-competent mice (r=0.615, P=0.015). Serum cholesterol and triglyceride levels were significantly lower in both male (63%, P=0.0005 and 57%, P=0.004) and female (73%, P=0.00009 and 54%, P=0.007) mast cell-deficient mice, with a concomitant decrease in atherogenic apoB-containing particles and serum prep-high-density lipoprotein and phospholipid transfer protein activity in both male (69% and 24%) and female (74% and 54%) mast cell-deficient mice. Serum soluble intercellular adhesion molecule was decreased in both male (32%, P=0.004) and female (28%, P=0.003) roast cell-deficient mice, whereas serum amyloid A was similar between mast cell-deficient and competent mice. In conclusion, mast cells participate in the pathogenesis of atherosclerosis in ldlr(-/-) mice by inducing both an atherogenic lipid profile and vascular inflammation. J. Cell. Biochem. 109: 615-623, 2010. (C) 2009 Wiley-Liss, Inc.