Cavoelin 1 Is Critical For-Abdominal Aortic Aneurysm Formation Induced By Angiotensin Ii And Inhibition Of Lysyl Oxidase
CLINICAL SCIENCE(2014)
Abstract
Although Angll (angiotensin II) and its receptor AT(1)R (Angll type 1 receptor) have been implicated in AAA (abdominal aortic aneurysm) formation, the proximal signalling events primarily responsible for AAA formation remain uncertain. Caveolae are cholesterol-rich membrane microdomains that serve as a signalling platform to facilitate the temporal and spatial localization of signal transduction events, including those stimulated by Angll. Cav1 (caveolin 1)-enriched caveolae in vascular smooth muscle cells mediate ADAM17 (a disintegrin and metalloproteinase 17)-dependent EGFR (epidermal growth factor receptor) transactivation, which is linked to vascular remodelling induced by Angll. In the present study, we have tested our hypothesis that Cav1 plays a critical role for the development of AAA at least in part via its specific alteration of Angll signalling within caveolae. Cav1(-/-) mice and the control wild-type mice were co-infused with Angll and beta-aminopropionitrile to induce MA. We found that Cav1(-/-) mice with the co-infusion did not develop AAA compared with control mice in spite of hypertension. We found an increased expression of ADAM17 and enhanced phosphorylation of EGFR in AAA. These events were markedly attenuated in Cav1(-/-) aortas with the co-infusion. Furthermore, aortas from Cav1(-/-) mice with the co-infusion showed less endoplasmic reticulum stress, oxidative stress and inflammatory responses compared with aortas from control mice. Cav1 silencing in cultured vascular smooth muscle cells prevented Angll-induced ADAM17 induction and activation. In conclusion, Cav1 appears to play a critical role in the formation of AM and associated endoplasmic reticulum/oxidative stress, presumably through the regulation of caveolae compartmentalized signals induced by Angll.
MoreTranslated text
Key words
abdominal aortic aneurysm, caveolae, hypertension, mouse model, signalling mechanism, vascular smooth muscle
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined