{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:02:58Z","timestamp":1791475378614,"version":"4.3.4"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,5,7]]},"abstract":"\n Background<\/jats:title>\n \n The mechanistic target of rapamycin complex 1 (\n mTORC<\/jats:styled-content>\n 1) is an important intracellular energy sensor that regulates gene expression and protein synthesis through its downstream signaling components, the S6\u2010kinase and the ribosomal S6 protein. Recently, signaling arising from\n mTORC<\/jats:styled-content>\n 1 has been implicated in regulation of the cardiovascular system with implications for disease. Here, we examined the contribution of\n mTORC<\/jats:styled-content>\n 1 signaling to the regulation of vascular function.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Activation of\n mTORC<\/jats:styled-content>\n 1 pathway in aortic rings with leucine or an adenoviral vector expressing a constitutively active S6\u2010kinase reduces endothelial\u2010dependent vasorelaxation in an\n mTORC<\/jats:styled-content>\n 1\u2010dependent manner without affecting smooth muscle relaxation responses. Moreover, activation of\n mTORC<\/jats:styled-content>\n 1 signaling in endothelial cells increases reactive oxygen species (\n ROS<\/jats:styled-content>\n ) generation and\n ROS<\/jats:styled-content>\n gene expression resulting in a pro\u2010oxidant gene environment. Blockade of\n ROS<\/jats:styled-content>\n signaling with Tempol restores endothelial function in vascular rings with increased\n mTORC<\/jats:styled-content>\n 1 activity indicating a crucial interaction between\n mTORC<\/jats:styled-content>\n 1 and\n ROS<\/jats:styled-content>\n signaling. We then tested the role of nuclear factor\u2010\u03baB transcriptional complex in connecting\n mTORC<\/jats:styled-content>\n 1 and\n ROS<\/jats:styled-content>\n signaling in endothelial cells. Blockade of inhibitor of nuclear factor \u03ba\u2010B kinase subunit \u03b2 activity with\n BMS<\/jats:styled-content>\n \u2010345541 prevented the increased\n ROS<\/jats:styled-content>\n generation associated with increased\n mTORC<\/jats:styled-content>\n 1 activity in endothelial cells but did not improve vascular endothelial function in aortic rings with increased\n mTORC<\/jats:styled-content>\n 1 and ROS signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These results implicate\n mTORC<\/jats:styled-content>\n 1 as a critical molecular signaling hub in the vascular endothelium in mediating vascular endothelial function through modulation of\n ROS<\/jats:styled-content>\n signaling.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.010662","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T09:20:54Z","timestamp":1556184054000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Mechanistic Target of Rapamycin Complex 1 Signaling Modulates Vascular Endothelial Function Through Reactive Oxygen Species"],"prefix":"10.1161","volume":"8","author":[{"given":"John J.","family":"Reho","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Iowa Carver College of Medicine Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng\u2010Fu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Iowa Carver College of Medicine Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Rahmouni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Iowa Carver College of Medicine Iowa City IA"},{"name":"Department of Internal Medicine University of Iowa Carver College of Medicine Iowa City IA"},{"name":"Fraternal Order of Eagles Diabetes Research Center University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20170219"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000131515.03336.f8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00497.2011"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.05.001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019237"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.02.017"},{"key":"e_1_3_2_8_2","first-page":"2959","article-title":"Activation of hypothalamic S6 kinase mediates diet\u2010induced hepatic insulin resistance in rats","volume":"118","author":"Ono H","year":"2008","unstructured":"Ono H, Pocai A, Wang Y, Sakoda H, Asano T, Backer JM, Schwartz GJ, Rossetti L. 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