Modulation of cutaneous wound healing by Losartan: A focus on MCP-1 activity and collagen synthesis

Losartan, a selective angiotensin II type 1 receptor (AT1R) antagonist, has shown anti-inflammatory and anti-fibrotic properties that may accelerate wound healing when applied topically. Impaired wound healing remains a global health concern, leading to chronic wounds, infection, and excessive scarring. This study is the first to evaluate the wound healing potential of topically applied Losartan.

Full-thickness excisional wounds were created on Sprague-Dawley rats and treated with topical Losartan (5 % or 10 %), base cream, or left untreated. Wound healing was assessed macroscopically and histologically at days 10, 20, and 30 post-injury. In addition to analyzing myeloperoxidase (MPO), monocyte chemotactic protein-1 (MCP-1), glycosaminoglycans (GAGs), and hydroxyproline, further parameters such as wound closure rate, collagen fiber alignment, revascularization, and inflammatory cell infiltration were evaluated.

Losartan-treated wounds showed significantly accelerated closure, enhanced cytokeratin 14 (CK14) and improved epithelial regeneration, and reduced inflammatory infiltration. MPO activity was notably decreased, especially in early healing, and MCP-1 modulation followed the macrophage dynamics. Histological results demonstrated enhanced fibroblast maturation, revascularization, and organized collagen deposition. Elevated levels of hydroxyproline and GAGs confirmed improved extracellular matrix formation.

This study is the first to demonstrate the efficacy of topically applied Losartan in promoting wound healing by modulating inflammation, enhancing matrix remodeling, and regulating CK14 expression. These findings support the therapeutic repositioning of Losartan as a novel topical agent and pave the way for its clinical development in the management of chronic wounds, including diabetic and ischemic ulcers.