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The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-surgical Adhesions

期刊

CURRENT PHARMACEUTICAL DESIGN
卷 28, 期 3, 页码 179-185

出版社

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612827666210625153011

关键词

Renin-Angiotensin system; ACEIs; ARBs; postsurgical adhesion; fibrosis; inflammation

资金

  1. Mashhad University of Medical Sciences, Iran

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This study provides an overview of using Renin-Angiotensin System (RAS) antagonists to treat post-surgical adhesion. The RAS signaling pathway has been found to play a significant role in inflammation, proliferation, and fibrosis pathways related to adhesion. Several FDA-approved drugs, such as telmisartan and valsartan, have shown promise in reducing fibrosis and improving adhesion after surgery.
Background: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, few improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered a blood pressure regulator. However, recent studies have indicated that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and wound healing. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion. Methods: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion. Results: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are used for targeting the RAS system, and some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including telmisartan, valsartan, and enalapril. Conclusion: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting the Renin-Angiotensin System may help to prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation.

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