Authors
Lian Tian, Danchen Wu, Asish Dasgupta, Kuang-Hueih Chen, Jeffrey Mewburn, Francois Potus, Patricia DA Lima, Zhigang Hong, Yuan-Yuan Zhao, Charles CT Hindmarch, Shelby Kutty, Steeve Provencher, Sebastien Bonnet, Gopinath Sutendra, Stephen L Archer
Publication date
2020/6/5
Journal
Circulation research
Volume
126
Issue
12
Pages
1723-1745
Publisher
Lippincott Williams & Wilkins
Description
Rationale
Right ventricular (RV) fibrosis in pulmonary arterial hypertension contributes to RV failure. While RV fibrosis reflects changes in the function of resident RV fibroblasts (RVfib), these cells are understudied.
Objective
Examine the role of mitochondrial metabolism of RVfib in RV fibrosis in human and experimental pulmonary arterial hypertension.
Methods and Results
Male Sprague-Dawley rats received monocrotaline (MCT; 60 mg/kg) or saline. Drinking water containing no supplement or the PDK (pyruvate dehydrogenase kinase) inhibitor dichloroacetate was started 7 days post-MCT. At week 4, treadmill testing, echocardiography, and right heart catheterization were performed. The effects of PDK activation on mitochondrial dynamics and metabolism, RVfib proliferation, and collagen production were studied in RVfib in cell culture. Epigenetic mechanisms for persistence of the profibrotic RVfib phenotype …
Scholar articles
L Tian, D Wu, A Dasgupta, KH Chen, J Mewburn… - Circulation research, 2020