The Critical Role of Dynamin-Related Protein 1 in Hypoxia-Induced Pulmonary Vascular Angiogenesis

Journal of Cellular Biochemistry
Tingting ShenDaling Zhu

Abstract

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by pulmonary vascular obstruction due in part to excessive pulmonary artery endothelial cells (PAECs) migration and proliferation. The mitochondrial fission protein dynamin-related protein-1 (DRP1) has important influence on pulmonary vascular remodeling. However, whether DRP1 participates in the development and progression of pulmonary vascular angiogenesis has not been reported previously. To test the hypothesis that DRP1 promotes the angiogenesis via promoting the proliferation, stimulating migration, and inhibiting the apoptosis of PAECs in mitochondrial Ca(2+)-dependent manner, we performed following studies. Using hemodynamic analysis and morphometric assay, we found that DRP1 mediated the elevation of right ventricular systemic pressure (RVSP), right heart hypertrophy, and increase of pulmonary microvessels induced by hypoxia. DRP1 inhibition reversed tube network formation in vitro stimulated by hypoxia. The mitochondrial Ca(2+) inhibited by hypoxia was recovered by DRP1 silencing. Moreover, pulmonary vascular angiogenesis promoted by DRP1 was reversed by the specific mitochondrial Ca(2+) uniporter inhibitor Ru360. In addition, DRP1 promoted the pro...Continue Reading

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Citations

Jul 15, 2017·Journal of Cellular Biochemistry·Min ZhangDaling Zhu
Oct 9, 2015·Journal of Cardiovascular Pharmacology·Ming-Xing LiYong Wang
Mar 10, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Da Yeon KimSang-Mo Kwon
May 18, 2017·Antioxidants·Sarbajeet Nagdas, David F Kashatus
Jun 1, 2020·Pharmacology & Therapeutics·Ayeshah A RosdahShiang Y Lim

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