Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3

• Autores: Solanki, Sumeet; Dube, Prabhatchandra R.; Birnbaumer, Lutz; Vazquez, Guillermo
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Scientific Reports. 2017;7:42526
• Materia: NECROSIS; APOPTOSIS; ARTERIOESCLEROSIS; MARCADORES BIOLOGICOS
• Institución: Pontificia Universidad Católica Argentina

Fil: Solanki, Sumeet. University of Toledo. College of Medicine and Life Sciences. Department of Physiology and Pharmacology. Center for Hypertension and Personalized Medicine; Estados Unidos
Fil: Dube, Prabhatchandra R. University of Toledo. College of Medicine and Life Sciences. Department of Physiology and Pharmacology. Center for Hypertension and Personalized Medicine; 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. Laboratory of Neurobiology; Estados Unidos
Fil: Vazquez, Guillermo. University of Toledo. College of Medicine and Life Sciences. Department of Physiology and Pharmacology. Center for Hypertension and Personalized Medicine; Estados Unidos
Abstract: In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr-/-) mice with macrophage-specific loss of Trpc3 (MacTrpc3-/-/Ldlr-/- → Ldlr-/-). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3-/-/Ldlr-/- → Ldlr-/- mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis.