Beyond blood pressure: the renin-angiotensin system as an innovative driver and therapeutic target in pathological scarring

Pathological scarring, a fibroproliferative disorder, imposes a substantial burden on affected individuals. This review explores the pivotal role of the local cutaneous renin-angiotensin system (RAS) in the pathogenesis of pathological scarring. We summarize evidence demonstrating how the pro-fibrotic angiotensin II/angiotensin II type 1 receptor (Ang II/AT1R) axis drives scar formation by promoting fibroblast proliferation, inflammation, and excessive extracellular matrix (ECM) deposition. Concurrently, we examine the interactions between RAS and other fibrotic pathways, as well as inflammation and reactive oxygen species (ROS). Importantly, the review highlights the significant therapeutic potential of targeting this pathway with RAS inhibitors-specifically angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-particularly in topical formulations. We also outline recent advances in next-generation RAS therapies. Finally, we summarize current limitations and challenges in clinical translation, emphasizing the need for advanced clinical trials and precision medicine strategies to facilitate its clinical adoption.