Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension

Rodríguez, Diego A.; Khilzi, Karys; Blanco, Isabel; Rodó-Pin, Anna; Martín-Ontiyuelo, Clara; Blasco, Anna Herranz; García-Lucio, Jéssica; Molina, Luís; Marco, Ester; Barreiro, Esther; Piccari, Lucilla; Peinado, Víctor I.; García, Antoni Trilla; Tura-Ceide, Olga; Barberà, Joan Albert

doi:10.3390/biomedicines11071822

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…Endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage repair. This effect could contribute to a positive hemodynamic and clinical response [ 179 ], as with HTN [ 180 ].…”

Section: Progress In Research and Treatment In Pah With The Potential...mentioning

confidence: 99%

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Sykora,

Szeiffova Bacova,

Andelova

et al. 2024

IJMS

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While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function.

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Section: Progress In Research and Treatment In Pah With The Potential...mentioning

confidence: 99%

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Sykora,

Szeiffova Bacova,

Andelova

et al. 2024

IJMS

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“…Improvements in endothelial function in PAH have been seen in human participants completing exercise training. Recently, it was shown that aerobic exercise training improved progenitor cells and the progenitor cell to endothelial microvesicle ratio (an important marker of endothelial damage and repair capacity) [57].…”

Section: Rationale For Exercise Training In Phmentioning

confidence: 99%

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

Poojary,

Morris,

Joshi

et al. 2024

Pulse

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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.

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Expanding horizons in pulmonary hypertension management: A systematic review and meta-analysis of non-pharmacological interventions

Albulushi,

De Silva,

Kashoub

et al. 2024

Current Problems in Cardiology

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Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension

Cited by 7 publications

References 35 publications

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

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

Expanding horizons in pulmonary hypertension management: A systematic review and meta-analysis of non-pharmacological interventions

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