{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:39:30Z","timestamp":1788586770041,"version":"build-2803163510"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">This study investigated whether gCTRP9 (globular C1q\/tumor necrosis factor\u2013related protein\u20109) could restore high\u2010glucose (HG)\u2010suppressed endothelial progenitor cell (EPC) functions by activating the endothelial nitric oxide synthase (eNOS).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">EPCs were treated with HG (25\u2009mmol\/L) and gCTRP9. Migration, adhesion, and tube formation assays were performed. Adiponectin receptor 1, adiponectin receptor 2, and N\u2010cadherin expression and AMP\u2010activated protein kinase, protein kinase B, and eNOS phosphorylation were measured by Western blotting. eNOS activity was determined using nitrite production measurement. In\u00a0vivo reendothelialization and EPC homing assays were performed using Evans blue and immunofluorescence in mice. Treatment with gCTRP9 at physiological levels enhanced migration, adhesion, and tube formation of EPCs. gCTRP9 upregulated the phosphorylation of AMP\u2010activated protein kinase, protein kinase B, and eNOS and increased nitrite production in a concentration\u2010dependent manner. Exposure of EPCs to HG\u2010attenuated EPC functions induced cellular senescence and decreased eNOS activity and nitric oxide synthesis; the effects of HG were reversed by gCTRP9. Protein kinase B knockdown inhibited eNOS phosphorylation but did not affect gCTRP9\u2010induced AMP\u2010activated protein kinase phosphorylation. HG impaired N\u2010cadherin expression, but treatment with gCTRP9 restored N\u2010cadherin expression after HG stimulation. gCTRP9 restored HG\u2010impaired EPC functions through both adiponectin receptor 1 and N\u2010cadherin\u2010mediated AMP\u2010activated protein kinase \/protein kinase B\/eNOS signaling. Nude mice that received EPCs treated with gCTRP9 under HG medium showed a significant enhancement of the reendothelialization capacity compared with those with EPCs incubated under HG conditions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">CTRP9 promotes EPC migration, adhesion, and tube formation and restores these functions under HG conditions through eNOS\u2010mediated signaling mechanisms. Therefore, CTRP9 modulation could eventually be used for vascular healing after injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.030054","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T10:42:41Z","timestamp":1707820961000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["C1q\/Tumor Necrosis Factor\u2013Related Protein\u20109 Is a Novel Vasculoprotective Cytokine That Restores High Glucose\u2010Suppressed Endothelial Progenitor Cell Functions by Activating the Endothelial Nitric Oxide Synthase"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7756-6620","authenticated-orcid":false,"given":"Qingsong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiology First Affiliated Hospital of Jinan University Guangzhou 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