title: The interaction of transient receptor potential melastatin 7 with macrophages promotes vascular adventitial remodeling in transverse aortic constriction rats.
abstract: Transient receptor potential melastatin 7 (TRPM7), a novel channel kinase, has been recently identified in the vasculature. However, its regulation and function in vascular diseases remain poorly understood. To address this lack of knowledge, we sought to examine whether TRPM7 can mediate the vascular remodeling process induced by pressure overload in the right common carotid artery proximal to the band (RCCA-B) in male Sprague-Dawley rats with transverse aortic constriction (TAC). The contribution of TRPM7 to amplified vascular remodeling after TAC was tested using morphometric and western blot analyses. Pressure overload-induced vascular wall thickening, especially in the adventitia, was readily detected in RCCA-B. The TRPM7 level was increased with a simultaneous accumulation of macrophages in the adventitia of RCCA-B, whereas the anti-inflammatory molecule annexin-1, a TRPM7 downstream target, was decreased. After the addition of the TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB), significant reductions in macrophage accumulation as well as the expression of monocyte chemotactic protein-1, SM-22-α and collagen I were observed, whereas annexin-1 was rescued. Finally, in cultured vascular adventitial fibroblasts treated with macrophage-conditioned medium, there were marked increases in the expression of TRPM7 and SM-22-α with a concurrent reduction in annexin-1 expression; these effects were largely prevented by treatment with 2-APB and specific anti-TRPM7 small interfering RNA. Our findings provide the first demonstration of the potential regulatory roles of TRPM7 in the vascular inflammation, pressure overload-mediated vascular adventitial collagen accumulation and cell phenotypic transformation in TAC rats. The targeting of TRPM7 has potential therapeutic importance for vascular diseases.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chengchao
authors.initials: C
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiuchang
authors.initials: J
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Pingjin
authors.initials: P
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dingliang
authors.initials: D
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D017302:Annexins / Q000378:metabolism; D001011:Aorta / Q000473:pathology / Q000502:physiology*; D015153:Blotting, Western; D017536:Carotid Artery, Common / Q000473:pathology; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D005347:Fibroblasts / Q000473:pathology; D006973:Hypertension / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D058628:Myofibroblasts / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D014657:Vasculitis / Q000473:pathology
chemical_list: D017302:Annexins; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; C486584:Trpm7 protein, rat