{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:04:20Z","timestamp":1771301060155,"version":"3.50.1"},"reference-count":83,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130014"],"award-info":[{"award-number":["82130014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81925003"],"award-info":[{"award-number":["81925003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92249304"],"award-info":[{"award-number":["92249304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270516"],"award-info":[{"award-number":["82270516"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070451"],"award-info":[{"award-number":["82070451"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Proper arteriogenesis after tissue ischaemia is necessary to rebuild stable blood circulation; nevertheless, this process is impaired in type 2 diabetes mellitus (T2DM). Raptor is a scaffold protein and a component of mammalian target of rapamycin complex 1 (mTORC1). However, the role of the endothelial Raptor in arteriogenesis under the conditions of T2DM remains unknown. This study investigated the role of endothelial Raptor in ischaemia-induced arteriogenesis during T2DM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Although endothelial mTORC1 is hyperactive in T2DM, we observed a marked reduction in the expression of endothelial Raptor in two mouse models and in human vessels. Inducible endothelial-specific Raptor knockout severely exacerbated impaired hindlimb perfusion and arteriogenesis after hindlimb ischaemic injury in 12-week high-fat diet fed mice. Additionally, we found that Raptor deficiency dampened vascular endothelial growth factor receptor 2 (VEGFR2) signalling in endothelial cells (ECs) and inhibited VEGF-induced cell migration and tube formation in a PTP1B-dependent manner. Furthermore, mass spectrometry analysis indicated that Raptor interacts with neuropilin 1 (NRP1), the co-receptor of VEGFR2, and mediates VEGFR2 trafficking by facilitating the interaction between NRP1 and Synectin. Finally, we found that EC-specific overexpression of the Raptor mutant (loss of mTOR binding) reversed impaired hindlimb perfusion and arteriogenesis induced by endothelial Raptor knockout in high-fat diet fed mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Collectively, our study demonstrated the crucial role of endothelial Raptor in promoting ischaemia-induced arteriogenesis in T2DM by mediating VEGFR2 signalling. Thus, endothelial Raptor is a novel therapeutic target for promoting arteriogenesis and ameliorating perfusion in T2DM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae105","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:22:36Z","timestamp":1715275356000},"page":"1218-1234","source":"Crossref","is-referenced-by-count":3,"title":["Role of endothelial Raptor in abnormal arteriogenesis after lower limb ischaemia in type 2 diabetes"],"prefix":"10.1093","volume":"120","author":[{"given":"Ting","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, The Second Hospital of Tianjin Medical University, Tianjin Medical University , Qixiangtai Rd 22nd, Tianjin 300070 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiachen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, The Second Hospital of Tianjin Medical University, Tianjin Medical University , Qixiangtai Rd 22nd, Tianjin 300070 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyuan","family":"Chang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, The Second Hospital of Tianjin Medical University, Tianjin Medical University , Qixiangtai Rd 22nd, Tianjin 300070 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medical Sciences, Tianjin Medical University , Tianjin 300070 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0772-1594","authenticated-orcid":false,"given":"Jinlong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Tianjin Medical University , Qixiangtai Rd 22nd, Tianjin 300070 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-9904","authenticated-orcid":false,"given":"Ding","family":"Ai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, The Second Hospital of Tianjin Medical University, Tianjin Medical University , Qixiangtai Rd 22nd, Tianjin 300070 , China"},{"name":"Department of Physiology and Pathophysiology, Tianjin Medical University , Qixiangtai Rd 22nd, Tianjin 300070 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"2024090216322793600_cvae105-B1","doi-asserted-by":"crossref","first-page":"j5842","DOI":"10.1136\/bmj.j5842","article-title":"Peripheral artery disease","volume":"360","author":"Morley","year":"2018","journal-title":"BMJ"},{"key":"2024090216322793600_cvae105-B2","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1161\/CIR.0000000000001005","article-title":"Lower extremity peripheral artery disease: contemporary epidemiology, management gaps, and future directions: a scientific statement from the American Heart Association","volume":"144","author":"Criqui","year":"2021","journal-title":"Circulation"},{"key":"2024090216322793600_cvae105-B3","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1001\/jama.2021.2126","article-title":"Lower extremity peripheral artery disease without chronic limb-threatening ischemia: a review","volume":"325","author":"Polonsky","year":"2021","journal-title":"JAMA"},{"key":"2024090216322793600_cvae105-B4","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1161\/ATVBAHA.120.314595","article-title":"Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease","volume":"40","author":"Barnes","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024090216322793600_cvae105-B5","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/s12916-022-02476-0","article-title":"Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians","volume":"20","author":"Xiu","year":"2022","journal-title":"BMC Med"},{"key":"2024090216322793600_cvae105-B6","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1161\/ATVBAHA.115.305775","article-title":"Mechanisms of amplified arteriogenesis in collateral artery segments exposed to reversed flow direction","volume":"35","author":"Heuslein","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024090216322793600_cvae105-B7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/74651","article-title":"Mechanisms of angiogenesis and arteriogenesis","volume":"6","author":"Carmeliet","year":"2000","journal-title":"Nat Med"},{"key":"2024090216322793600_cvae105-B8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/dmrr.2232","article-title":"Arteriogenesis versus angiogenesis in peripheral artery disease","volume":"28","author":"Troidl","year":"2012","journal-title":"Diabetes Metab Res Rev"},{"key":"2024090216322793600_cvae105-B9","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<338::AID-PATH594>3.0.CO;2-7","article-title":"The pathophysiology of the collateral circulation (arteriogenesis)","volume":"190","author":"Buschmann","year":"2000","journal-title":"J Pathol"},{"key":"2024090216322793600_cvae105-B10","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1161\/01.RES.0000141145.78900.44","article-title":"Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis)","volume":"95","author":"Heil","year":"2004","journal-title":"Circ Res"},{"key":"2024090216322793600_cvae105-B11","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.jacc.2005.06.007","article-title":"Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease","volume":"46","author":"Sasso","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2024090216322793600_cvae105-B12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1042\/CS20100082","article-title":"Diabetes impairs arteriogenesis in the peripheral circulation: review of molecular mechanisms","volume":"119","author":"Ruiter","year":"2010","journal-title":"Clin Sci (Lond)"},{"key":"2024090216322793600_cvae105-B13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrm.2016.87","article-title":"Mechanisms and regulation of endothelial VEGF receptor signalling","volume":"17","author":"Simons","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024090216322793600_cvae105-B14","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in signaling and disease: beyond discovery and development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"2024090216322793600_cvae105-B15","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1046\/j.1523-1755.1999.00610.x","article-title":"Role of vascular endothelial growth factor in the regulation of angiogenesis","volume":"56","author":"Ferrara","year":"1999","journal-title":"Kidney Int"},{"key":"2024090216322793600_cvae105-B16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nrm1911","article-title":"VEGF receptor signalling\u2014in control of vascular function","volume":"7","author":"Olsson","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024090216322793600_cvae105-B17","first-page":"213","article-title":"An inside view: VEGF receptor trafficking and signaling","volume":"27","author":"Simons","year":"2012","journal-title":"Physiology (Bethesda)"},{"key":"2024090216322793600_cvae105-B18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/ncb2679","article-title":"Spatial regulation of VEGF receptor endocytosis in angiogenesis","volume":"15","author":"Nakayama","year":"2013","journal-title":"Nat Cell Biol"},{"key":"2024090216322793600_cvae105-B19","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.devcel.2010.02.016","article-title":"VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis","volume":"18","author":"Lanahan","year":"2010","journal-title":"Dev Cell"},{"key":"2024090216322793600_cvae105-B20","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 signaling and the metabolic control of cell growth","volume":"45","author":"Ben-Sahra","year":"2017","journal-title":"Curr Opin Cell Biol"},{"key":"2024090216322793600_cvae105-B21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024090216322793600_cvae105-B22","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"2024090216322793600_cvae105-B23","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.3390\/ijms19072043","article-title":"Role of mTOR in glucose and lipid metabolism","volume":"19","author":"Mao","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2024090216322793600_cvae105-B24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.tibs.2004.11.003","article-title":"Restraining PI3K: mTOR signalling goes back to the membrane","volume":"30","author":"Harrington","year":"2005","journal-title":"Trends Biochem Sci"},{"key":"2024090216322793600_cvae105-B25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0092-8674(02)00833-4","article-title":"Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action","volume":"110","author":"Hara","year":"2002","journal-title":"Cell"},{"key":"2024090216322793600_cvae105-B26","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.cell.2013.07.031","article-title":"Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells","volume":"154","author":"Thedieck","year":"2013","journal-title":"Cell"},{"key":"2024090216322793600_cvae105-B27","doi-asserted-by":"crossref","first-page":"10255","DOI":"10.1038\/ncomms10255","article-title":"mTORC1-independent raptor prevents hepatic steatosis by stabilizing PHLPP2","volume":"7","author":"Kim","year":"2016","journal-title":"Nat Commun"},{"key":"2024090216322793600_cvae105-B28","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1161\/CIRCRESAHA.114.302313","article-title":"Disruption of mammalian target of rapamycin complex 1 in macrophages decreases chemokine gene expression and atherosclerosis","volume":"114","author":"Ai","year":"2014","journal-title":"Circ Res"},{"key":"2024090216322793600_cvae105-B29","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1161\/HYPERTENSIONAHA.119.12834","article-title":"Regulation of YAP by mammalian target of rapamycin complex 1 in endothelial cells controls blood pressure through COX-2\/mPGES-1\/PGE(2) cascade","volume":"74","author":"Yao","year":"2019","journal-title":"Hypertension"},{"key":"2024090216322793600_cvae105-B30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41467-019-14076-3","article-title":"Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis","volume":"11","author":"Fu","year":"2020","journal-title":"Nat Commun"},{"key":"2024090216322793600_cvae105-B31","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.devcel.2013.03.019","article-title":"The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis","volume":"25","author":"Lanahan","year":"2013","journal-title":"Dev Cell"},{"key":"2024090216322793600_cvae105-B32","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1161\/CIRCULATIONAHA.105.542829","article-title":"Delayed arteriogenesis in hypercholesterolemic mice","volume":"112","author":"Tirziu","year":"2005","journal-title":"Circulation"},{"key":"2024090216322793600_cvae105-B33","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1161\/ATVBAHA.109.192732","article-title":"Mapping 3-dimensional neovessel organization steps using micro-computed tomography in a murine model of hindlimb ischemia-brief report","volume":"29","author":"Oses","year":"2009","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024090216322793600_cvae105-B34","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1172\/JCI91770","article-title":"Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy","volume":"127","author":"Zhu","year":"2017","journal-title":"J Clin Invest"},{"key":"2024090216322793600_cvae105-B35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41556-021-00822-7","article-title":"Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis","volume":"24","author":"Das","year":"2022","journal-title":"Nat Cell Biol"},{"key":"2024090216322793600_cvae105-B36","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1038\/s41467-019-10359-x","article-title":"Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis","volume":"10","author":"Genet","year":"2019","journal-title":"Nat Commun"},{"key":"2024090216322793600_cvae105-B37","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1161\/CIRCRESAHA.120.316857","article-title":"Coupling of integrin alpha5 to annexin A2 by flow drives endothelial activation","volume":"127","author":"Zhang","year":"2020","journal-title":"Circ Res"},{"key":"2024090216322793600_cvae105-B38","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1038\/s41467-021-23408-1","article-title":"The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2","volume":"12","author":"Ash","year":"2021","journal-title":"Nat Commun"},{"key":"2024090216322793600_cvae105-B39","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1161\/CIRCRESAHA.117.311950","article-title":"Yes-associated protein promotes angiogenesis via signal transducer and activator of transcription 3 in endothelial cells","volume":"122","author":"He","year":"2018","journal-title":"Circ Res"},{"key":"2024090216322793600_cvae105-B40","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1152\/physrev.00026.2020","article-title":"Regulation and metabolic functions of mTORC1 and mTORC2","volume":"101","author":"Szwed","year":"2021","journal-title":"Physiol Rev"},{"key":"2024090216322793600_cvae105-B41","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1210\/en.2004-0921","article-title":"Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance","volume":"146","author":"Khamzina","year":"2005","journal-title":"Endocrinology"},{"key":"2024090216322793600_cvae105-B42","first-page":"918267","article-title":"Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing","volume":"2012","author":"Kolluru","year":"2012","journal-title":"Int J Vasc Med"},{"key":"2024090216322793600_cvae105-B43","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1128\/MCB.00306-14","article-title":"Regulation of endothelial cell proliferation and vascular assembly through distinct mTORC2 signaling pathways","volume":"35","author":"Wang","year":"2015","journal-title":"Mol Cell Biol"},{"key":"2024090216322793600_cvae105-B44","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1161\/CIRCRESAHA.107.160630","article-title":"Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1","volume":"101","author":"Hazarika","year":"2007","journal-title":"Circ Res"},{"key":"2024090216322793600_cvae105-B45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12964-020-00681-z","article-title":"Histone deacetylase 3 inhibition alleviates type 2 diabetes mellitus-induced endothelial dysfunction via Nrf2","volume":"19","author":"Huang","year":"2021","journal-title":"Cell Commun Signal"},{"key":"2024090216322793600_cvae105-B46","doi-asserted-by":"crossref","first-page":"101811","DOI":"10.1016\/j.redox.2020.101811","article-title":"aFGF alleviates diabetic endothelial dysfunction by decreasing oxidative stress via Wnt\/\u03b2-catenin-mediated upregulation of HXK2","volume":"39","author":"Sun","year":"2021","journal-title":"Redox Biol"},{"key":"2024090216322793600_cvae105-B47","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1161\/CIRCULATIONAHA.114.009683","article-title":"PTP1b is a physiologic regulator of vascular endothelial growth factor signaling in endothelial cells","volume":"130","author":"Lanahan","year":"2014","journal-title":"Circulation"},{"key":"2024090216322793600_cvae105-B48","doi-asserted-by":"crossref","first-page":"D529","DOI":"10.1093\/nar\/gky1079","article-title":"The BioGRID interaction database: 2019 update","volume":"47","author":"Oughtred","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2024090216322793600_cvae105-B49","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1161\/ATVBAHA.114.303217","article-title":"Receptor tyrosine kinases endocytosis in endothelium: biology and signaling","volume":"34","author":"Zhang","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024090216322793600_cvae105-B50","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0092-8674(02)00808-5","article-title":"mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery","volume":"110","author":"Kim","year":"2002","journal-title":"Cell"},{"key":"2024090216322793600_cvae105-B51","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1182\/blood-2011-01-328773","article-title":"Neuropilin-1 promotes VEGFR-2 trafficking through Rab11 vesicles thereby specifying signal output","volume":"118","author":"Ballmer-Hofer","year":"2011","journal-title":"Blood"},{"key":"2024090216322793600_cvae105-B52","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.devcel.2006.03.012","article-title":"Selective regulation of arterial branching morphogenesis by synectin","volume":"10","author":"Chittenden","year":"2006","journal-title":"Dev Cell"},{"key":"2024090216322793600_cvae105-B53","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nature20602","article-title":"Integrin-YAP\/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow","volume":"540","author":"Wang","year":"2016","journal-title":"Nature"},{"key":"2024090216322793600_cvae105-B54","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1161\/CIRCRESAHA.113.301340","article-title":"Endothelial cell-dependent regulation of arteriogenesis","volume":"113","author":"Moraes","year":"2013","journal-title":"Circ Res"},{"key":"2024090216322793600_cvae105-B55","doi-asserted-by":"crossref","first-page":"758158","DOI":"10.3389\/fcvm.2021.758158","article-title":"Activated protein C ameliorates diabetic cardiomyopathy via modulating OTUB1\/YB-1\/MEF2B axis","volume":"8","author":"Zhong","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2024090216322793600_cvae105-B56","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41418-022-01047-3","article-title":"Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, raptor","volume":"30","author":"Seo","year":"2023","journal-title":"Cell Death Differ"},{"key":"2024090216322793600_cvae105-B57","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41419-023-05884-z","article-title":"Cathepsin K inhibition induces raptor destabilization and mitochondrial dysfunction via Syk\/SHP2\/Src\/OTUB1 axis-mediated signaling","volume":"14","author":"Seo","year":"2023","journal-title":"Cell Death Dis"},{"key":"2024090216322793600_cvae105-B58","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.freeradbiomed.2017.05.001","article-title":"Endothelial deletion of mTORC1 protects against hindlimb ischemia in diabetic mice via activation of autophagy, attenuation of oxidative stress and alleviation of inflammation","volume":"108","author":"Fan","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"2024090216322793600_cvae105-B59","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1161\/ATVBAHA.121.315805","article-title":"Heme oxy genase-1 in macrophages impairs the perfusion recovery after hindlimb ischemia by suppressing autolysosome-dependent degradation of NLRP3","volume":"41","author":"Ma","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024090216322793600_cvae105-B60","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/380435a0","article-title":"Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele","volume":"380","author":"Carmeliet","year":"1996","journal-title":"Nature"},{"key":"2024090216322793600_cvae105-B61","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1634\/theoncologist.2014-0465","article-title":"Targeting angiogenesis in cancer therapy: moving beyond vascular endothelial growth factor","volume":"20","author":"Zhao","year":"2015","journal-title":"Oncologist"},{"key":"2024090216322793600_cvae105-B62","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1242\/dev.103028","article-title":"Neuropilin 1 (NRP1) hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis","volume":"141","author":"Fantin","year":"2014","journal-title":"Development"},{"key":"2024090216322793600_cvae105-B63","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1042\/BST20110689","article-title":"Neuropilin signalling in angiogenesis","volume":"40","author":"Koch","year":"2012","journal-title":"Biochem Soc Trans"},{"key":"2024090216322793600_cvae105-B64","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0092-8674(00)81402-6","article-title":"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor","volume":"92","author":"Soker","year":"1998","journal-title":"Cell"},{"key":"2024090216322793600_cvae105-B65","doi-asserted-by":"crossref","first-page":"25520","DOI":"10.1074\/jbc.M102315200","article-title":"Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121)","volume":"276","author":"Whitaker","year":"2001","journal-title":"J Biol Chem"},{"key":"2024090216322793600_cvae105-B66","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1038\/onc.2010.139","article-title":"Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy","volume":"29","author":"Sparks","year":"2010","journal-title":"Oncogene"},{"key":"2024090216322793600_cvae105-B67","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.preteyeres.2016.02.003","article-title":"NRP1 function and targeting in neurovascular development and eye disease","volume":"52","author":"Raimondi","year":"2016","journal-title":"Prog Retin Eye Res"},{"key":"2024090216322793600_cvae105-B68","doi-asserted-by":"crossref","first-page":"246","DOI":"10.2174\/1568026619666190201152153","article-title":"PTP1b inhibition, a promising approach for the treatment of diabetes type II","volume":"19","author":"Eleftheriou","year":"2019","journal-title":"Curr Top Med Chem"},{"key":"2024090216322793600_cvae105-B69","doi-asserted-by":"crossref","first-page":"e03720","DOI":"10.7554\/eLife.03720","article-title":"Neuropilin-1 functions as a VEGFR2 co-receptor to guide developmental angiogenesis independent of ligand binding","volume":"3","author":"Gelfand","year":"2014","journal-title":"Elife"},{"key":"2024090216322793600_cvae105-B70","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1007\/s00125-006-0439-5","article-title":"Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice","volume":"49","author":"Korsheninnikova","year":"2006","journal-title":"Diabetologia"},{"key":"2024090216322793600_cvae105-B71","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.2337\/diabetes.54.9.2674","article-title":"Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability","volume":"54","author":"Tremblay","year":"2005","journal-title":"Diabetes"},{"key":"2024090216322793600_cvae105-B72","doi-asserted-by":"crossref","first-page":"14056","DOI":"10.1073\/pnas.0706517104","article-title":"Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance","volume":"104","author":"Tremblay","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024090216322793600_cvae105-B73","doi-asserted-by":"crossref","first-page":"14959","DOI":"10.1038\/srep14959","article-title":"Paradoxical effect of rapamycin on inflammatory stress-induced insulin resistance in vitro and in vivo","volume":"5","author":"Yang","year":"2015","journal-title":"Sci Rep"},{"key":"2024090216322793600_cvae105-B74","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s00125-004-1662-6","article-title":"Regulation of insulin signalling by hyperinsulinaemia: role of IRS-1\/2 serine phosphorylation and the mTOR\/p70 S6K pathway","volume":"48","author":"Ueno","year":"2005","journal-title":"Diabetologia"},{"key":"2024090216322793600_cvae105-B75","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1126\/science.1215135","article-title":"Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity","volume":"335","author":"Lamming","year":"2012","journal-title":"Science"},{"key":"2024090216322793600_cvae105-B76","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2337\/db07-0922","article-title":"mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes","volume":"57","author":"Fraenkel","year":"2008","journal-title":"Diabetes"},{"key":"2024090216322793600_cvae105-B77","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.2337\/db09-1324","article-title":"Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue","volume":"59","author":"Houde","year":"2010","journal-title":"Diabetes"},{"key":"2024090216322793600_cvae105-B78","doi-asserted-by":"crossref","first-page":"186215","DOI":"10.1155\/2013\/186215","article-title":"Gene therapy and cell-based therapies for therapeutic angiogenesis in peripheral artery disease","volume":"2013","author":"Shimamura","year":"2013","journal-title":"Biomed Res Int"},{"key":"2024090216322793600_cvae105-B79","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1067\/mva.2002.123677","article-title":"Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial","volume":"35","author":"Comerota","year":"2002","journal-title":"J Vasc Surg"},{"key":"2024090216322793600_cvae105-B80","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1161\/01.CIR.0000093398.16124.29","article-title":"Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication","volume":"108","author":"Rajagopalan","year":"2003","journal-title":"Circulation"},{"key":"2024090216322793600_cvae105-B81","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/gt.2010.51","article-title":"Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia","volume":"17","author":"Shigematsu","year":"2010","journal-title":"Gene Ther"},{"key":"2024090216322793600_cvae105-B82","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/S0741-5214(98)70022-9","article-title":"Treatment of thromboangiitis obliterans (Buerger\u2019s disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results","volume":"28","author":"Isner","year":"1998","journal-title":"J Vasc Surg"},{"key":"2024090216322793600_cvae105-B83","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/hum.2006.17.683","article-title":"Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial","volume":"17","author":"Kusumanto","year":"2006","journal-title":"Hum Gene Ther"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvae105\/57830837\/cvae105.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/120\/10\/1218\/58997041\/cvae105.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/120\/10\/1218\/58997041\/cvae105.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T19:00:09Z","timestamp":1725303609000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/120\/10\/1218\/7667836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":83,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5,9]]},"published-print":{"date-parts":[[2024,9,2]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvae105","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,5,9]]}}}