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The Renin-Angiotensin System in Cutaneous Hypertrophic Scar and Keloid Formation Publisher Pubmed



Hedayatyanfard K1, 2 ; Haddadi NS2, 3 ; Ziai SA4 ; Karim H2 ; Niazi F5 ; Steckelings UM6 ; Habibi B4 ; Modarressi A7 ; Dehpour AR3
Authors
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Authors Affiliations
  1. 1. Evidence-Based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran
  2. 2. Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Iran
  5. 5. Department of Plastic and Reconstructive Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. Institute for Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
  7. 7. Department of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Switzerland

Source: Experimental Dermatology Published:2020


Abstract

Hypertrophic scar and keloid are two types of fibroproliferative conditions that result from excessive extracellular matrix production. The underlying pathological mechanism is not entirely clear. Activation of the renin-angiotensin system (RAS) is associated with fibrosis in various organs. RAS components including angiotensin II (Ang II), angiotensin AT1 and AT2 receptors, and angiotensin-converting enzyme (ACE) are expressed in the skin and act independently from the plasma RAS. AT1 receptors, which are usually the dominating receptor subtype, promote fibrosis and scar formation, while AT2 receptors inhibit the aforementioned AT1 receptor-coupled effects. Elevated angiotensin II (Ang II) levels acting on the AT1 receptor contribute to skin scar formation through increased expression of inflammatory factors such as interleukin-6 (IL-6), angiogenic factors such as vascular endothelial growth factor (VEGF) and fibrinogenic factors such as transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF), while at the same time suppressing the anti-fibrotic tissue inhibitors of matrix metalloproteinase (TIMPs). First, small clinical trials have provided evidence that inhibition of the ACE/Ang II/ AT1 receptor axis may be effective in the treatment of hypertrophic scars/keloids. This review provides a detailed overview of the current literature on the RAS in skin, wound healing and scar formation and discusses the translational potential of targeting this hormonal system for treatment and prevention of hypertrophic scars and keloids. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd