Cardiac Fibroblast-Specific Knockout of PGC-1α Accelerates AngII-Induced Cardiac Remodeling

Hong-Jin Chen; Xiao-Xi Pan; Li-Li-Qiang Ding; Cheng-Chao Ruan; Ping-Jin Gao

doi:10.3389/fcvm.2021.664626

Cardiac Fibroblast-Specific Knockout of PGC-1α Accelerates AngII-Induced Cardiac Remodeling

Front Cardiovasc Med. 2021 Jun 16:8:664626. doi: 10.3389/fcvm.2021.664626. eCollection 2021.

Authors

Hong-Jin Chen¹, Xiao-Xi Pan¹, Li-Li-Qiang Ding¹, Cheng-Chao Ruan², Ping-Jin Gao¹

Affiliations

¹ Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Abstract

Cardiac remodeling consisted of ventricular hypertrophy and interstitial fibrosis is the pathological process of many heart diseases. Fibroblasts as one of the major cells in the myocardium regulate the balance of the generation and degeneration of collagen, and these cells transform toward myofibroblasts in pathological state, contributing to the remodeling of the heart. Peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α) is vital to the function of mitochondria, which contributes to the energy production and reactive oxidative species (ROS)-scavenging activity in the heart. In this study, we found that fibroblast-specific PGC-1α KO induced cardiac remodeling especially fibrosis, and Angiotensin II (AngII) aggravated cardiac fibrosis, accompanied with a high level of oxidative stress response and inflammation.

Keywords: AngII; PGC-1α; cardiac fibroblast; cardiac remodeling; fibrosis.