Supplementary Material for: Role of exercise in pulmonary hypertension: Evidence from bench to bedside

Background: Pulmonary hypertension (PH) is a debilitating condition characterized by elevated pulmonary arterial pressure and progressive vascular remodeling, leading to exercise intolerance. The progression of PAH is regulated at a cellular and molecular level which influences various physiological processes. Exercise plays an important role in improving function in PH. Although the signalling pathways that regulate cardio-protection through exercise have not been fully understood, the positive impact of exercise on the various physiological systems are well established. Summary: Exercise has emerged as a potential adjunctive therapy for PH, with growing evidence supporting its beneficial effects on various aspects of the disease pathophysiology. This review highlights the contributions of cellular and molecular pathways and physiological processes to exercise intolerance. Preclinical studies have provided insight into the mechanisms underlying exercise-induced improvements in PH which are modulated through improvements in endothelial function, inflammation, oxidative stress, and mitochondrial function. Along with preclinical studies, various clinical studies have demonstrated that exercise training can lead to significant improvements in exercise capacity, hemodynamics, quality of life, and functional status. Moreover, exercise interventions have been shown to improve skeletal muscle function, and enhance pulmonary vascular remodeling, contributing to overall disease management. Further research efforts aimed at better understanding the role of exercise in PH pathophysiology and refining exercise interventions are warranted to realize its full potential in the management of this complex disease. Key messages: Despite the promising benefits of exercise in PH, several challenges remain, including the optimal intensity, duration, and type of exercise training, as well as patient selection criteria and long-term adherence. Additionally, the mechanisms underlying the observed improvements require further elucidation to optimize exercise protocols and personalize treatment strategies. Nonetheless, exercise represents a promising therapeutic approach that can complement existing pharmacological therapies and improve outcomes in PH patients.