z-logo
open-access-imgOpen Access
Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3
Author(s) -
S. K. Solanki,
Prabhatchandra Dube,
Lutz Birnbaumer,
Guillermo Vázquez
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep42526
Subject(s) - trpc3 , macrophage , apoptosis , necrosis , biology , tumor necrosis factor alpha , cancer research , immunology , pathology , medicine , receptor , in vitro , biochemistry , transient receptor potential channel , trpc
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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here