Resistin-Like Molecule α Dysregulates Cardiac Bioenergetics in Neonatal Rat Cardiomyocytes

Frontiers in Cardiovascular Medicine

Qing Lin¹  Wei Dong Gao¹  John Skinner¹  Ailan Zhang¹  Roger A. Johns¹  Santosh Kumar¹  Chunling Fan¹  Elizabeth Hunter¹  Jose Gomez-Arroyo¹  Kazuyo Yamaji-Kegan²  Bingdong Tao³  Wenqian Zhai⁴  Idris Samad⁵  Alexander T. Hillel⁵ 

[1] Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States;Department of Anesthesiology, Maryland University, School of Medicine, Baltimore, MD, United States;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States;Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States;Department of Anesthesiology, Tianjin Chest Hospital, Tianjin, China;Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States;

关键词: fatty acid oxidation;    mitochondria;    RELMα;    heart failiure;    oxygen consumption rate;   

DOI  :  10.3389/fcvm.2021.574708

来源: Frontiers

【 摘 要 】

Heart (right) failure is the most frequent cause of death in patients with pulmonary arterial hypertension. Although historically, increased right ventricular afterload has been considered the main contributor to right heart failure in such patients, recent evidence has suggested a potential role of load-independent factors. Here, we tested the hypothesis that resistin–like molecule α (RELMα), which has been implicated in the pathogenesis of vascular remodeling in pulmonary artery hypertension, also contributes to cardiac metabolic remodeling, leading to heart failure. Recombinant RELMα (rRELMα) was generated via a Tet-On expression system in the T-REx 293 cell line. Cultured neonatal rat cardiomyocytes were treated with purified rRELMα for 24 h at a dose of 50 nM. Treated cardiomyocytes exhibited decreased mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and transcription factors PPARα and ERRα, which regulate mitochondrial fatty acid metabolism, whereas genes that encode for glycolysis-related proteins were significantly upregulated. Cardiomyocytes treated with rRELMα also exhibited a decreased basal respiration, maximal respiration, spare respiratory capacity, ATP-linked OCR, and increased glycolysis, as assessed with a microplate-based cellular respirometry apparatus. Transmission electron microscopy revealed abnormal mitochondrial ultrastructure in cardiomyocytes treated with rRELMα. Our data indicate that RELMα affects cardiac energy metabolism and mitochondrial structure, biogenesis, and function by downregulating the expression of the PGC-1α/PPARα/ERRα axis.

【 授权许可】

CC BY