{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:41:05Z","timestamp":1765485665936},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Increased cardiac stromal cell-derived factor-1\u03b1 (SDF-1\u03b1) expression promotes neovascularization and myocardial repair after ischemic injury through recruiting stem cells and reducing cardiomyocyte death. Previous studies have shown that heme oxygenase-1 and its reaction byproduct, carbon monoxide (CO), induce SDF-1\u03b1 expression in ischemic heart. However, the mechanism underlying heme oxygenase-1\/CO-induced cardiac SDF-1\u03b1 expression remains elusive. This study aims to investigate the signaling pathway and the transcriptional factor that mediate CO-induced SDF-1\u03b1 gene expression and cardioprotection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>CO gas and a CO-releasing compound, tricarbonyldichlororuthenium (II) dimer, dose-dependently induced SDF-1\u03b1 expression in primary neonatal cardiomyocytes and H9C2 cardiomyoblasts. Promoter luciferase-reporter assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation demonstrated that the activator protein 2\u03b1 (AP-2\u03b1) mediated tricarbonyldichlororuthenium (II) dimer-induced SDF-1\u03b1 gene transcription. Tricarbonyldichlororuthenium (II) dimer induced AP-2\u03b1 expression via protein kinase B (AKT)-dependent signaling. AKT inhibition or AP-2\u03b1 knockdown reduced tricarbonyldichlororuthenium (II) dimer-induced SDF-1\u03b1 expression. Coronary ligation induced transient increases of cardiac AP-2\u03b1 and SDF-1\u03b1 expression, which were declined at 1 week postinfarction in mice. Periodic exposure of coronary-ligated mice to CO (250 ppm for 1 hour\/day, 6 days) resumed the induction of AP-2\u03b1 and SDF-1\u03b1 gene expression in infarcted hearts. Immunohistochemistry and echocardiography performed at 4 weeks after coronary ligation revealed that CO treatment enhanced neovascularization in the myocardium of peri-infarct region and improved cardiac function. CO-mediated SDF-1\u03b1 expression and cardioprotection was ablated by intramyocardial injection of lentivirus bearing specific short hairpin RNA targeting AP-2\u03b1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our data demonstrate that AKT-dependent upregulation of AP-2\u03b1 is essential for CO-induced SDF-1\u03b1 expression and myocardial repair after ischemic injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.301143","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T09:00:21Z","timestamp":1360314021000},"page":"785-794","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Activator Protein-2\u03b1 Mediates Carbon Monoxide\u2013Induced Stromal Cell\u2013Derived Factor-1\u03b1 Expression and Vascularization in Ischemic Heart"],"prefix":"10.1161","volume":"33","author":[{"given":"Heng-Huei","family":"Lin","sequence":"first","affiliation":[{"name":"From the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Tsai","family":"Chiang","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee-Young","family":"Chau","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1998.0128"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1400"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14232-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000147780.30124.cf"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.672451"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6558com"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.082453"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.107.07104"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.12.1695"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh1401.093314"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00133.2002"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc0502.103363"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000120152.27263.87"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.04.011"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.02.050"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.905471"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.23.8643-8654.2000"},{"key":"e_1_3_3_19_2","first-page":"3730","article-title":"The CO\/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy.","volume":"117","author":"Suliman HB","year":"2007","unstructured":"Suliman HB, Carraway MS, Ali AS, Reynolds CM, Welty-Wolf KE, Piantadosi CA. 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