Reversal of right ventricular remodeling by dichloroacetate is related to inhibition of mitochondria-dependent apoptosis

Hypertension Research : Official Journal of the Japanese Society of Hypertension
Xiao-Qing SunZhi-Cheng Jing

Abstract

Most patients with pulmonary arterial hypertension die from right ventricular failure (RVF). Right ventricular (RV) myocardial apoptosis has an important role in RVF and is regulated by the mitochondria. Dichloroacetate (DCA) can improve cardiac function in RVF, but whether it can regulate myocardial apoptosis via mitochondria is still unknown. In this study, we investigated the effects of DCA on myocardial mitochondria, the mitochondrial apoptosis and other aspects of RV remodeling, including fibrosis and capillary rarefaction. RVF was induced in rats by a single s.c. injection of monocrotaline. After 4 weeks, DCA treatment was started with i.p. injection of 50, 150 or 2007 mg kg(-1) per day during 14 days. Compared with saline-treated RVF animals, treatment with DCA resulted in decreased mean pulmonary arterial pressure and total pulmonary resistance (TPR), and increased cardiac output. The expression of pyruvate dehydrogenase kinase was suppressed, while pyruvate dehydrogenase expression was upregulated with DCA application. DCA treatment was also associated with restored RV mitochondrial function and a reduction in RV hypertrophy, fibrosis, capillary rarefaction and apoptosis. Mitochondria-dependent apoptosis was involved i...Continue Reading

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Citations

Sep 2, 2016·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Qiang GuoJian-An Huang
Feb 2, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Matthew K HensleyYen-Chun Lai
May 11, 2017·Journal of Cellular Physiology·Zhe ChenLinxi Chen
Jun 1, 2018·American Journal of Respiratory Cell and Molecular Biology·Brian B GrahamRubin M Tuder
Dec 19, 2018·American Journal of Hypertension·Yun-Long ZhangZhi-Cheng Jing
Apr 4, 2019·Pulmonary Circulation·Xianfeng RenWei Dong Gao
Aug 5, 2016·American Journal of Physiology. Cell Physiology·Anastasia FamiltsevaSuresh C Tyagi
Aug 28, 2019·Journal of the American Heart Association·Masaki KajimotoMichael A Portman
Mar 30, 2017·Therapeutic Advances in Chronic Disease·Jessica B Badlam, Todd M Bull
Jan 16, 2021·Free Radical Biology & Medicine·Danchen WuStephen L Archer
Aug 25, 2020·ACS Pharmacology & Translational Science·Monika SpaczyńskaEduardo Oliver

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