Macrophage (drp1) dynamin-related protein 1 accelerates intimal thickening after vascular injury

Ryuta Umezu, Jun Ichiro Koga, Tetsuya Matoba, Shunsuke Katsuki, Lixiang Wang, Nao Hasuzawa, Masatoshi Nomura, Hiroyuki Tsutsui, Kensuke Egashira

研究成果: Contribution to journalArticle査読

6 被引用数 (Scopus)

抄録

Objective: Mitochondria consistently change their morphology in a process regulated by proteins, including Drp1 (dynaminrelated protein 1), a protein promoting mitochondrial fission. Drp1 is involved in the mechanisms underlying various cardiovascular diseases, such as myocardial ischemia/reperfusion injury, heart failure, and pulmonary arterial hypertension. However, its role in macrophages, which promote various vascular diseases, is poorly understood. We therefore tested our hypothesis that macrophage Drp1 promotes vascular remodeling after injury. Method and Results: To explore the selective role of macrophage Drp1, we created macrophage-selective Drp1-deficient mice and performed femoral arterial wire injury. In these mice, intimal thickening and negative remodeling were attenuated at 4 weeks after injury when compared with control mice. Deletion of macrophage Drp1 also attenuated the macrophage accumulation and cell proliferation in the injured arteries. Gain- and loss-of-function experiments using cultured macrophages indicated that Drp1 induces the expression of molecules associated with inflammatory macrophages. Morphologically, mitochondrial fission was induced in inflammatory macrophages, whereas mitochondrial fusion was induced in less inflammatory/reparative macrophages. Pharmacological inhibition or knockdown of Drp1 decreased the mitochondrial reactive oxygen species and chemotactic activity in cultured macrophages. Co-culture experiments of macrophages with vascular smooth muscle cells indicated that deletion of macrophage Drp1 suppresses growth and migration of vascular smooth muscle cells induced by macrophage-derived soluble factors. Conclusions: Macrophage Drp1 accelerates intimal thickening after vascular injury by promoting macrophage-mediated inflammation. Macrophage Drp1 may be a potential therapeutic target of vascular diseases.

本文言語英語
ページ(範囲)E214-E226
ジャーナルArteriosclerosis, thrombosis, and vascular biology
40
7
DOI
出版ステータス出版済み - 7 2020

All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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