Pathogenic and therapeutic significance of angiotensin II type I receptor in abdominal aortic aneurysms. Current drug targets Xu, B., Xuan, H., Iida, Y., Miyata, M., Dalman, R. L. 2018


BACKGROUND: Abdominal aortic aneurysm (AAA) is a chronic degenerative inflammatory disease. Multi-factors including genetic, environmental and lifestyles determine the onsets and progression of AAAs. Currently surgical repair remains the only effective aneurysm treatment, but no pharmacological therapy is available for limiting further enlargement of small AAAs and fetal rupture.OBJECTIVE: This article is to review our current understanding of angiotensin II (Ang II) and its type 1 receptor (AT1) in AAA pathogenesis as well as the translational potential of AT1 receptor blocker (ARB) treatment for treating clinical AAA disease.RESULTS: While many pathways or molecules have been shown to associate with AAA formation and progression, accumulating evidence indicates the most significant importance of peptide hormone angiotensin II (Ang II) and its type 1 receptor (AT1) in AAA pathogenesis and suggest the translational value of targeting inhibition of AT1 in treating clinical AAA disease. This review summarized the influences of genetic angiotensin II type 1 (AT1) receptor deficiency and pharmacological AT1 receptor blocker (ARB) treatment on experimental AAAs. A discussion has also been made on whether and how ARB medication in AAA patients changes the natural course of clinical AAAs, including aneurysm enlargement rate, rupture and AAA-specific mortality. Additionally, we provided information on two registered clinical trials which are to test the efficacy of telmisartan and valsartan in limiting small AAA enlargement.CONCLUSIONS: Ang II/AT1 pathway plays a critical role in aneurysmal pathogenesis. Targeting AT1 via ARB will help establishing novel pharmacological therapies for limiting continuous enlargement of small AAAs in patients.

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