{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T08:13:38Z","timestamp":1769328818640,"version":"3.49.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec><jats:title>Objective\u2014<\/jats:title><jats:p>Angiotensin II (Ang II) is implicated in processes underlying the development of arterial wall remodeling events, including cellular hypertrophy and inflammation. We previously documented the activation of I\u03baB kinase-\u03b2 (IKK\u03b2) in Ang II\u2013treated cells, a kinase involved in inflammatory reactions. In light of a study suggesting a role of IKK\u03b2 in angiogenesis through its effect on the tuberous sclerosis (TSC)1\/2\u2013mammalian target of rapamycin complex 1 pathway in cancer cells, we hypothesized that targeting IKK\u03b2 could reduce arterial remodeling events by affecting both the inflammatory and the growth-promoting response of Ang II.<\/jats:p><\/jats:sec><jats:sec><jats:title>Approach and Results\u2014<\/jats:title><jats:p>Treatment of aortic vascular smooth muscle cells with Ang II induced the rapid and sustained phosphorylation of TSC1 on Ser511, which paralleled the activation of effectors of the mammalian target of rapamycin complex 1 pathway. Furthermore, we show that Ser511 of TSC1 acted as a phosphoacceptor site for Ang II\u2013activated IKK\u03b2. Consistent with this, the use of different short hairpin RNA constructs targeting IKK\u03b2 reduced Ang II\u2013induced TSC1, S6 kinase, and eukaryotic translation initiation factor 4E\u2013binding protein 1 phosphorylation and the rate of protein synthesis. Overexpression of TSC1 lacking Ser511 in vascular smooth muscle cells also exerted detrimental effects on the hypertrophic effect of Ang II. Furthermore, the selective IKK\u03b2 inhibitor<jats:italic>N<\/jats:italic>-(6-chloro-7-methoxy-9H-\u03b2-carbolin-8-yl)-2 methylnicotinamide reduced the inflammatory response and dose-dependently diminished Ang II\u2013induced TSC1 phosphorylation and effectors of the mammalian target of rapamycin complex 1 pathway, leading to inhibition of protein synthesis in vitro and in rat arteries in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2014<\/jats:title><jats:p>Our findings provide new insights into the molecular understanding of the pathological role of Ang II and assist in identifying the beneficial effects of IKK\u03b2 inhibition for the treatment of cardiovascular diseases.<\/jats:p><\/jats:sec>","DOI":"10.1161\/atvbaha.113.302487","type":"journal-article","created":{"date-parts":[[2013,10,18]],"date-time":"2013-10-18T04:16:32Z","timestamp":1382069792000},"page":"2850-2857","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Role of I\u03baB Kinase-\u03b2 in the Growth-Promoting Effects of Angiotensin II In Vitro and In Vivo"],"prefix":"10.1161","volume":"33","author":[{"given":"Priscilla","family":"Doyon","sequence":"first","affiliation":[{"name":"From the Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy J.","family":"van Zuylen","sequence":"additional","affiliation":[{"name":"From the Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc J.","family":"Servant","sequence":"additional","affiliation":[{"name":"From the Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00287.2006"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399411001815"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.05.003"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-012110-142315"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.126433"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512815200"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000190589.52286.41"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132641"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104227200"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.10.3549-3561.2002"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00302-2"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.10.3886-3895.2005"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408061101"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.058"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204009"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00220-X"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2009.12.001"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb839"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.031"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.055"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.27.16047"},{"key":"e_1_3_5_23_2","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/S0026-895X(25)10509-9","article-title":"Involvement of a tyrosine kinase pathway in the growth-promoting effects of angiotensin II on aortic smooth muscle cells.","volume":"48","author":"Leduc I","year":"1995","unstructured":"Leduc I, Haddad P, Giasson E, Meloche S. 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