Targeting Corin and Furin in Hypertension and Heart Failure: A New Therapeutic Frontier in Cardiovascular Therapeutics.

Corin and furin are protetic enzymes central to the activation of natriuretic peptides (NPs), which regulate cardiovascular homeostasis. Recent insights suggest that disruptions in the Corin-Furin axis-via genetic polymorphisms, aberrant post-translational modifications, or disease-associated downregulation-contribute to the pathogenesis of hypertension, heart failure, and myocardial fibrosis. This study examines current challenges in enzymatic stability, pharmacodynamics, and delivery of corin- and furin-based therapies, emphasizing translational barriers and the need for precision medicine. We review preclinical models demonstrating the therapeutic promise of recombinant corin and furin inhibitors, as well as the limitations posed by species-specificity, short half-lives, and incomplete pharmacogenomic data. Multiomics platforms and systems biology approaches are highlighted as essential tools for identifying actionable targets, guiding patient stratification, and integrating corin genotyping into clinical care. Emerging strategies include engineered proteases, small-molecule modulators, and RNA-based interventions aimed at restoring proteolytic balance and enhancing NP signaling. While clinical application remains nascent, these findings underscore the therapeutic potential of targeting local NP-processing mechanisms. A comprehensive understanding of corin and furin function, regulation, and interactomes is critical for developing personalized interventions in cardiovascular disease.