3 years ago

Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds.

John Harmon, Joshua Budman, Neal Fedarko, Mahya Faghih, Tadashi Inagami, David Rini, Jing Tian, Sayed Hosseini, Diep Vuong, Guy Marti, Aleksandra Beselman, Peter Abadir, Jeremy Walston, Amir Ansari, Kevin Keenahan, Frank Lay, Barbara Smith, Alan Berger
Chronic wounds are among the most devastating and difficult to treat consequences of diabetes. Dysregulation of the skin renin-angiotensin system (RAS) is implicated in abnormal wound healing in diabetic and older adults. Given this, we sought to determine the effects of topical reformulations of the angiotensin type 1 receptor blockers (ARB) losartan and valsartan and the angiotensin-converting enzyme (ACE) inhibitor captopril on wound healing in diabetic and aged mice with further validation in older diabetic pigs. Application of 1% valsartan gel compared to other tested formulations and placebo facilitated and significantly accelerated closure time and increased tensile strength in mice, and was validated in the porcine model. 1% Valsartan gel-treated wounds also exhibited higher mitochondrial content, collagen deposition, phosphorylated SMAD2 and 3 and Co-SMAD4, αSMA, CD31, phospho-VEGF receptor 2, and p42/44 MAPK. Knockout of the angiotensin subtype 2 receptors (AT2R) abolished the beneficial effects of ARBs, suggesting a role for AT2R in chronic wound healing.

Publisher URL: http://doi.org/10.1016/j.jid.2017.09.030

DOI: 10.1016/j.jid.2017.09.030

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