Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary arterial wall remodeling, right ventricular (RV) hypertrophy, and interstitial fibrosis, ultimately culminating in RV failure. The latter is the strong predictor of mortality in PAH. While current therapies primarily target the pulmonary vasculature and reduce RV afterload, they do not directly address the metabolic and structural maladaptation of the RV. Emerging evidence indicates that cardiometabolic reprogramming occurs in the RV of PAH patients, encompassing dysregulated glucose, lipid, and amino acid metabolism. These metabolic dysregulations are mirrored in preclinical models, where cardiomyocytes, endothelial cells, and fibroblasts exhibit reduced fatty acid oxidation, enhanced glycolysis, and altered mitochondrial function. Such alterations may promote cardiomyocyte lipotoxicity, impair contractile efficiency, disrupt endothelial barrier integrity, facilitate monocyte recruitment, and drive fibroblast proliferation and activation, collectively contributing to RV inflammation, fibrosis, and functional decline. Understanding these cellspecific metabolic reprogramming is critical, as they may represent both compensatory and pathogenic mechanisms during the progression from RV adaptation to maladaptation. This review provides a comprehensive overview of recent advances in elucidating metabolic dysregulation in the RV of PAH patients and relevant in vivo and in vitro models. The therapeutic potential of targeting these pathways using metabolic modulators, small molecules, and natural products is also discussed, with the goal of developing RV-directed therapies that complement existing PAH treatments and improve patient outcomes.
关键词:
肺动脉高压;右心室纤维化;右心室失代偿;代谢调节剂;天然产物
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This work was supported in part by the NIH grant R01HL166327, an Institutional Development Award (IDeA) from the NIGMS of NIH under grant P30GM149398. The views expressed in this article are those of the authors and do not reflect the position or policy of the Department of Veterans Affairs or the US Federal Government.
Guanghui Qian a, b, Peng Zhang a, b, Gaurav Choudhary a, b, Hongwei Yao a, b,c,?. Cardiometabolic reprogramming in pulmonary arterial hypertension:Implications for right ventricular dysfunction and therapeutic strategies[J]. Chinese Herbal Medicines (CHM),2026,18(3):515-527
