Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds

J Invest Dermatol. 2018 Feb;138(2):434-443. doi: 10.1016/j.jid.2017.09.030. Epub 2017 Oct 24.


Chronic wounds are among the most devastating and difficult to treat consequences of diabetes. Dysregulation of the skin renin-angiotensin system 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 losartan and valsartan and the angiotensin-converting enzyme inhibitor captopril on wound healing in diabetic and aged mice with further validation in older diabetic pigs. The application of 1% valsartan gel compared with other tested formulations and placebo facilitated and significantly accelerated closure time and increased tensile strength in mice, and was validated in the porcine model. One percent of valsartan gel-treated wounds also exhibited higher mitochondrial content, collagen deposition, phosphorylated mothers against decapentaplegic homologs 2 and 3 and common mothers against decapentaplegic homolog 4, alpha-smooth muscle actin, CD31, phospho-vascular endothelial growth factor receptor 2, and p42/44 mitogen-activated protein kinase. Knockout of the angiotensin subtype 2 receptors abolished the beneficial effects of angiotensin type 1 receptor blockers, suggesting a role for angiotensin subtype 2 receptors in chronic wound healing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Administration, Cutaneous
  • Alloxan / toxicity
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Captopril / therapeutic use
  • Chronic Disease / drug therapy
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Angiotensin, Type 1 / genetics
  • Skin / injuries*
  • Skin / pathology
  • Swine
  • Swine, Miniature
  • Time Factors
  • Treatment Outcome
  • Valsartan / pharmacology
  • Valsartan / therapeutic use*
  • Wound Healing / drug effects
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / etiology
  • Wounds and Injuries / pathology


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Receptor, Angiotensin, Type 1
  • Alloxan
  • Valsartan
  • Captopril