title: Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3.
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.
authors.affiliation: Department of Physiology and Pharmacology, and Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, University of Toledo Health Science Campus, 3000 Transverse Dr., Toledo, Ohio 43614, USA.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Solanki
authors.affiliation: Department of Physiology and Pharmacology, and Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, University of Toledo Health Science Campus, 3000 Transverse Dr., Toledo, Ohio 43614, USA.
authors.forename: Prabhatchandra R
authors.initials: PR
authors.lastname: Dube
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, 111 TW Alexander Dr., Research Triangle Park, North Carolina 27709, USA.|Institute of Biomedical Research (BIOMED UCA-CONICET), Faculty of Medical Sciences, Av. Alicia Moreau de Justo 1600, C1107AFF, Buenos, Aires, Argentina.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Department of Physiology and Pharmacology, and Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, University of Toledo Health Science Campus, 3000 Transverse Dr., Toledo, Ohio 43614, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Vazquez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics; D050052:TRPC Cation Channels / Q000172:deficiency*
chemical_list: D015415:Biomarkers; D011973:Receptors, LDL; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel