{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:55:54Z","timestamp":1783464954150,"version":"3.55.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"NIH","award":["1K99HL128787-01A1"],"award-info":[{"award-number":["1K99HL128787-01A1"]}]},{"name":"NIH","award":["P01 HL112730"],"award-info":[{"award-number":["P01 HL112730"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:p> The objective of the present study was to 1) analyze the ascending aortic proteome within a mouse model of Marfan syndrome (MFS; Fbn1<jats:sup>C1041G\/+<\/jats:sup>) at early and late stages of aneurysm and 2) subsequently test a novel hypothesis formulated on the basis of this unbiased proteomic screen that links changes in integrin composition to transforming growth factor (TGF)-\u03b2-dependent activation of the rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling pathway. Ingenuity Pathway Analysis of over 1,000 proteins quantified from the in vivo MFS mouse aorta by data-independent acquisition mass spectrometry revealed a predicted upstream regulator, Rictor, that was selectively activated in aged MFS mice. We validated this pattern of Rictor activation in vivo by Western blot analysis for phosphorylation on Thr<jats:sup>1135<\/jats:sup> in a separate cohort of mice and showed in vitro that TGF-\u03b2 activates Rictor in an integrin-linked kinase-dependent manner in cultured aortic vascular smooth muscle cells. Expression of \u03b2<jats:sub>3<\/jats:sub>-integrin was upregulated in the aged MFS aorta relative to young MFS mice and wild-type mice. We showed that \u03b2<jats:sub>3<\/jats:sub>-integrin expression and activation modulated TGF-\u03b2-induced Rictor phosphorylation in vitro, and this signaling effect was associated with an altered vascular smooth muscle cell proliferative-migratory and metabolic in vitro phenotype that parallels the in vivo aneurysm phenotype in MFS. These results reveal that Rictor is a novel, context-dependent, noncanonical TGF-\u03b2 signaling effector with potential pathogenic implications in aortic aneurysm. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY We present the most comprehensive quantitative analysis of the ascending aortic aneurysm proteome in Marfan syndrome to date resulting in novel and potentially wide-reaching findings that expression and signaling by \u03b2<jats:sub>3<\/jats:sub>-integrin constitute a modulator of transforming growth factor-\u03b2-induced rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling and physiology in aortic vascular smooth muscle cells. <\/jats:p>","DOI":"10.1152\/ajpheart.00089.2018","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T10:40:59Z","timestamp":1531478459000},"page":"H1112-H1126","source":"Crossref","is-referenced-by-count":32,"title":["Proteomics reveals Rictor as a noncanonical TGF-\u03b2 signaling target during 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