Metabolic theory of pulmonary arterial hypertension: connecting mitochondrial roles with disease control

Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricular pressure overload and can lead to right-sided heart failure and death. A close link between PAH and cancer has been extensively suggested, with increasing evidence of a me...

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Autores principales: Nogueira de Alencar, Allan Kardec, Ferreira Cruz, Fernanda, Macedo Rocco, Patricia Rieken, Leme Silva, Pedro
Formato: Articulo
Lenguaje:Inglés
Publicado: 2022
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/140980
https://pmr.safisiol.org.ar/wp-content/uploads/2022/04/vol_15_numero_1__2022.pdf
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Sumario:Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricular pressure overload and can lead to right-sided heart failure and death. A close link between PAH and cancer has been extensively suggested, with increasing evidence of a metabolic theory that underlies the pathogenesis of both diseases, mainly due to similarities in the processes responsible for triggering a hyperproliferative and apoptosis-resistant phenotype in both cardiopulmonary and malignant cells. Similar to cancer, abnormalities in mitochondrial biogenesis might lead to the following consequences: dysfunction of this organelle, which, in turn, causes the Warburg effect, a shift from mitochondrial respiration toward glycolysis, culminating in mitophagy in diseased pulmonary vessels and right ventricular cardiomyocytes. The role of these mitochondrial abnormalities offers new therapeutic avenues. Therefore, this study reviews the bases of mitochondrial derangements in PAH and explores the therapeutic implications of mitochondrial dysfunction and metabolic disturbances in cells from the pulmonary vasculature and right ventricular myocardium by addressing promising and challenging areas of investigation.