Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3

BIRNBAUMER, LUTZ; VAZQUEZ, GUILLERMO; DUBE, PRABHATCHANDRA R.; CHIKKAMENAHALLI, LAKSHMIKANTH L.

ATHEROSCLEROSIS

ELSEVIER IRELAND LTD

Año: 2018 vol. 270 p. 199 - 204

0021-9150

Background and aims: Recent in vitro studies have showed that in macrophages, deletion of the nonselectiveCa2þ-permeable channel TRPC3 impairs expression of the osteogenic protein BMP-2. Thepathophysiological relevance of this effect in atherosclerotic plaque calcification remains to bedetermined.Methods: We used Ldlr/ mice with macrophage-specific loss of TRPC3 (MacTrpc3//Ldlr/) toexamine the effect of macrophage Trpc3 on plaque calcification and osteogenic features in advancedatherosclerosis.Results: After 25 weeks on high fat diet, aortic root plaques in MacTrpc3//Ldlr/ mice showed reducedsize, lipid and macrophage content compared to controls. Plaque calcification was decreased inMacTrpc3//Ldlr/ mice, and this was accompanied by marked reduction in BMP-2, Runx-2 andphospho-SMAD1/5 contents within macrophage-rich areas. Expression of Bmp-2 and Runx-2 was alsoreduced in bone marrow-derived macrophages from MacTrpc3//Ldlr/ mice.Conclusions: These findings show that, in advanced atherosclerosis, selective deletion of TRPC3 inmacrophages favors plaque regression and impairs the activity of a novel macrophage-associated, BMP2-dependentmechanism of calcification.