Matrix metalloproteinases and tissue inhibitors of metalloproteinases as potential biomarkers for pulmonary arterial hypertension: A review

Pulmonary arterial hypertension (PAH) is a rare and progressive syndrome that is frequently diagnosed at an advanced stage due to the nonspecific nature of its symptoms. Current research aims to identify novel diagnostic tools, including biomarkers, to facilitate earlier detection and differentiation of pulmonary hypertension (PH) subtypes. Matrix metalloproteinases (MMPs) play a critical role in the pathogenesis of PAH through extracellular matrix (ECM) remodeling, with their activity tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). This review summarizes existing studies on the potential of MMPs and TIMPs as biomarkers for PAH. Our analysis highlights significant differences in MMP concentrations between PAH patients and healthy controls. In particular, MMP-2, MMP-7 and MMP-9 exhibit promising prognostic value, which could contribute to risk stratification and support clinical decision-making in the future. However, large-scale, randomized prospective studies involving well-characterized patient cohorts are necessary to confirm their clinical utility and clarify their mechanistic roles in PAH pathogenesis.