Unraveling the pathogenesis of viral-induced pulmonary arterial hypertension: Possible new therapeutic avenues with mesenchymal stromal cells and their derivatives.

Abstract

Pulmonary hypertension (PH) is a severe condition characterized by elevated pressure in the pulmonary artery, where metabolic and mitochondrial dysfunction may contribute to its progression. Within the PH spectrum, pulmonary arterial hypertension (PAH) stands out with its primary pulmonary vasculopathy. PAH's prevalence varies from 0.4 to 1.4 per 100,000 individuals and is associated with diverse conditions, including viral infections such as HIV. Notably, recent observations highlight an increased occurrence of PAH among COVID-19 patients, even in the absence of pre-existing cardiopulmonary disorders. While current treatments offer partial relief, there's a pressing need for innovative therapeutic strategies, among which mesenchymal stromal cells (MSCs) and their derivatives hold promise. This review critically evaluates recent investigations into viral-induced PAH, encompassing pathogens like human immunodeficiency virus, herpesvirus, Cytomegalovirus, Hepatitis B and C viruses, SARS-CoV-2, and Human endogenous retrovirus K (HERKV), with a specific emphasis on mitochondrial dysfunction. Furthermore, we explore the underlying rationale driving novel therapeutic modalities, including MSCs, extracellular vesicles, and mitochondrial interventions, within the framework of PAH management.