Highlights
- •TRPC3 is a component of a novel mechanism that stimulates plaque calcification.
- •A macrophage-associated, BMP-2 dependent process stimulates plaque calcification.
- •First evidence suggesting that macrophages retain ability to produce BMP-2 in vivo.
Abstract
Background and aims
Recent in vitro studies have showed that in macrophages, deletion of the non-selective Ca2+-permeable channel TRPC3 impairs expression of the osteogenic protein BMP-2. The pathophysiological
relevance of this effect in atherosclerotic plaque calcification remains to be determined.
Methods
We used Ldlr−/− mice with macrophage-specific loss of TRPC3 (MacTrpc3−/−/Ldlr−/−) to examine the effect of macrophage Trpc3 on plaque calcification and osteogenic
features in advanced atherosclerosis.
Results
After 25 weeks on high fat diet, aortic root plaques in MacTrpc3−/−/Ldlr−/− mice showed reduced size, lipid and macrophage content compared to controls. Plaque
calcification was decreased in MacTrpc3−/−/Ldlr−/− mice, and this was accompanied by marked reduction in BMP-2, Runx-2 and phospho-SMAD1/5
contents within macrophage-rich areas. Expression of Bmp-2 and Runx-2 was also reduced
in bone marrow-derived macrophages from MacTrpc3−/−/Ldlr−/− mice.
Conclusions
These findings show that, in advanced atherosclerosis, selective deletion of TRPC3
in macrophages favors plaque regression and impairs the activity of a novel macrophage-associated,
BMP-2-dependent mechanism of calcification.
Keywords
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Article Info
Publication History
Published online: December 21, 2017
Accepted:
December 15,
2017
Received in revised form:
December 14,
2017
Received:
September 9,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
