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 of 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 prebeta-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) mast 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.
Heikkilä
Hanna M
HM
Wihuri Research Institute, Kalliolinnantie 4, FI-00140 Helsinki, Finland.
Trosien
Julia
J
Metso
Jari
J
Jauhiainen
Matti
M
Pentikäinen
Markku O
MO
Kovanen
Petri T
PT
Lindstedt
Ken A
KA
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D014657:Vasculitis / Q000209:etiology / Q000378:metabolism
D008074:Lipoproteins; D011973:Receptors, LDL