Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
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 b...
Guardado en:
| Autores principales: | , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2019
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| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/8715 |
| Aporte de: |
| Sumario: | 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 macrophageassociated, BMP-2-dependent mechanism of calcification. |
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