Purpose: The mechanisms underlying abdominal aortic aneurysms (AAAs) are still not fully understood, previous researches showed ADAM17 is increased in aneurysm. We hypothesized that inhibiting ADAM17 can decrease AAA formation and progression. Materials and methods: Aneurysm models were established in mouses and rats by aortic adventitial CaCl_2 incubation and aortic pericardial patch angioplasty respectively. In mouse, control (no treatment) or SA/HA hydrogel loaded with TAPI-1 (ADAM17 inhibitor) were adventitial applied; in rat, control and TAPI-1 coated pericardial patch were used in rat aortic pericardial patch angioplasty. Samples were harvested on day 14 or 30 and analyzed by immunofluorescence. Bioinformatics analysis and immunostaining analysis were carried out to confirm the therapeutic potential of ADAM17 in the human AAA. Results: ADAM17 was highly expressed in mouses, rats and human aneurysms. Adventitial application of SA/HA hydrogel loaded TAPI-1 or TAPI-1 conjugated pericardial patch can decrease AAA formation and progression in mouses and rats, respectively. Bioinformatic analysis showed ADAM1 7 promotes transformation of M1 macro-phages and synthetic vascular smooth muscle cells, together with immunostaining analysis and results from animal models, the therapeutic potential of ADAM17 in the human AAA were confirmed. Conclusion: We showed that local delivery of ADAM17 inhibitor can inhibit aneurysm formation and progression in mouse and rat, these results showed ADAM17 plays an important role in the aneurysm formation and may be a potential treatment target.
ADAM17AneurysmSmooth muscle cellsMacrophage
Hualong Bai、Liwei Zhang、Peng Sun、Haoliang Wu、Mingxing Li、Yulei Gu、Cong Zhang、Chunyang Lou、Jing'an Li
展开 >
Department of Vascular and Endovascular Surgery, First Affiliated Hospital ofZhengzhou University
NSTL
