The renin-angiotensin system in cutaneous hypertrophic scar and keloid formation

Keshvad Hedayatyanfard, Nazgol-Sadat Haddadi, Seyed Ali Ziai, Hossein Karim, Feizollah Niazi, U Muscha Steckelings, Behnam Habibi, Ali Modarressi, Ahmad Reza Dehpour

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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.

TidsskriftExperimental Dermatology
StatusE-pub ahead of print - 17. jul. 2020

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  • Citationsformater

    Hedayatyanfard, K., Haddadi, N-S., Ziai, S. A., Karim, H., Niazi, F., Steckelings, U. M., Habibi, B., Modarressi, A., & Dehpour, A. R. (2020). The renin-angiotensin system in cutaneous hypertrophic scar and keloid formation. Experimental Dermatology.