| First Author | Solanki S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 42526 | PubMed ID | 28186192 |
| Mgi Jnum | J:275152 | Mgi Id | MGI:6296222 |
| Doi | 10.1038/srep42526 | Citation | Solanki S, et al. (2017) Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3. Sci Rep 7:42526 |
| abstractText | 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. |
