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

• Autores: Dube, Prabhatchandra R.; Chikkamenahalli, Lakshmikanth L.; Birnbaumer, Lutz; Vazquez, Guillermo
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Atherosclerosis. 2018;270:199-204.
• Materia: ARTERIOESCLEROSIS; CALCIFICACION; OSTEOGENESIS; FOSFORILACION
• Institución: Pontificia Universidad Católica Argentina

Fil: Dube, Prabhatchandra R. University of Toledo. College of Medicine and Life Sciences. Center for Hypertension and Personalized Medicine. Department of Physiology and Pharmacology; Estados Unidos
Fil: Chikkamenahalli, Lakshmikanth L. University of Toledo. College of Medicine and Life Sciences. Center for Hypertension and Personalized Medicine. Department of Physiology and Pharmacology; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Research Triangle Park. Neurobiology Laboratory; Estados Unidos
Fil: Vazquez, Guillermo. University of Toledo. College of Medicine and Life Sciences. Center for Hypertension and Personalized Medicine. Department of Physiology and Pharmacology; Estados Unidos
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.