A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind‐Limb Ischemia

Tsukasa Shimauchi, Takuro Numaga‐tomita, Yuri Kato, Hiroyuki Morimoto, Kosuke Sakata, Ryosuke Matsukane, Akiyuki Nishimura, Kazuhiro Nishiyama, Atsushi Shibuta, Yutoku Horiuchi, Hitoshi Kurose, Sang Geon Kim, Yasuteru Urano, Takashi Ohshima, Motohiro Nishida

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Retarded revascularization after progressive occlusion of large conductance arteries is a major cause of bad prognosis for peripheral artery disease (PAD). However, pharmacological treatment for PAD is still limited. We previously reported that suppression of transient receptor potential canonical (TRPC) 6 channel activity in vascular smooth muscle cells (VSMCs) facilitates VSMC differentiation without affecting proliferation and migration. In this study, we found that 1−benzilpiperadine derivative (1−BP), a selective inhibitor for TRPC3 and TRPC6 channel activities, induced VSMC differentiation. 1‐ BP‐treated mice showed increased capillary arterialization and improvement of peripheral circulation and skeletal muscle mass after hind‐limb ischemia (HLI) in mice. 1−BP had no additive effect on the facilitation of blood flow recovery after HLI in TRPC6−deficient mice, suggesting that suppression of TRPC6 underlies facilitation of the blood flow recovery by 1−BP. 1−BP also improved vascular nitric oxide bioavailability and blood flow recovery after HLI in hypercholesterolemic mice with endothelial dysfunction, suggesting the retrograde interaction from VSMCs to endothelium. These results suggest that 1−BP becomes a potential seed for PAD treatments that target vascular TRPC6 channels.

本文言語英語
論文番号2041
ジャーナルCells
11
13
DOI
出版ステータス出版済み - 7月 1 2022

!!!All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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