Metabolic Alterations Associated With Right Ventricular Dysfunction in Pulmonary Arterial Hypertension: The Modulatory Effects and Improvement Mechanisms of Exercise.

Abstract

Pulmonary arterial hypertension (PAH) is characterized by a significant increase in pulmonary arterial pressure, leading to right ventricular failure (RVF), limited exercise capacity, and increased mortality risk. Right ventricular function is a critical determinant of exercise capacity and prognosis in patients with PAH. Meanwhile, alterations in cellular metabolism and bioenergy are common features in PAH, with the differential regulation of metabolic pathways playing a significant role in right ventricular dysfunction (RVD). Mitochondria, essential organelles responsible for energy production, biosynthetic pathways, and signal transduction, are particularly implicated in differential regulation. Exercise is increasingly recognized as a beneficial adjunct therapy; however, specific recommendations are often lacking in official guidelines. This review examines the changes in metabolic pathways associated with RVD in PAH, including glycolysis, glucose oxidation, fatty acid oxidation, glutamine metabolism, and arginine metabolism. Furthermore, this article discusses how exercise can modulate the aforementioned metabolic pathways to improve metabolic disturbances in the right ventricle and enhance right heart function. These are essential for developing effective rehabilitation strategies.