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.
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.
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.
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.