{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T22:27:58Z","timestamp":1778797678118,"version":"3.51.4"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,9,18]]},"abstract":"\n Background<\/jats:title>\n \n The present study demonstrates that the ubiquitin E3 ligase, Pellino\u20101 (Peli1), is an important angiogenic molecule under the control of vascular endothelial growth factor (VEGF) receptor 2\/Flk\u20101. We have previously reported increased survivability of ischemic skin flap tissue by adenovirus carrying Peli1 (Ad\u2010Peli1) gene therapy in Flk\u20101\n +\/\u2212<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Two separate experimental groups of mice were subjected to myocardial infarction (\n MI<\/jats:styled-content>\n ) followed by the immediate intramyocardial injection of adenovirus carrying LacZ (Ad\u2010LacZ) (1\u00d710\n 9<\/jats:sup>\n \u00a0pfu) or Ad\u2010Peli1 (1\u00d710\n 9<\/jats:sup>\n \u00a0pfu). Heart tissues were collected for analyses. Compared with wild\u2010type (\n WTMI<\/jats:styled-content>\n ) mice, analysis revealed decreased expressions of Peli1, phosphorylated (p\u2010)Flk\u20101, p\u2010Akt, p\u2010\n eNOS<\/jats:styled-content>\n , p\u2010\n MK<\/jats:styled-content>\n 2, p\u2010I\u03baB\u03b1, and\n NF<\/jats:styled-content>\n \u2010\u03baB and decreased vessel densities in Flk\u20101\n +\/\u2212<\/jats:sup>\n mice subjected to\n MI<\/jats:styled-content>\n (Flk\u20101\n +\/\u2212<\/jats:sup>\n MI<\/jats:styled-content>\n ). Mice (\n CD<\/jats:styled-content>\n 1) treated with Ad\u2010Peli1 after the induction of\n MI<\/jats:styled-content>\n showed increased \u03b2\u2010catenin translocation to the nucleus, connexin 43 expression, and phosphorylation of Akt,\n eNOS<\/jats:styled-content>\n ,\n MK<\/jats:styled-content>\n 2, and I\u03baB\u03b1, that was followed by increased vessel densities compared with the Ad\u2010LacZ\u2013treated group. Echocardiography conducted 30\u00a0days after surgery showed decreased function in the Flk1\n +\/\u2212<\/jats:sup>\n MI<\/jats:styled-content>\n group compared with\n WTMI<\/jats:styled-content>\n , which was restored by Ad\u2010Peli1 gene therapy. In addition, therapy with Ad\u2010Peli1 stimulated angiogenic and arteriogenic responses in both\n CD<\/jats:styled-content>\n 1 and Flk\u20101\n +\/\u2212<\/jats:sup>\n mice following\n MI<\/jats:styled-content>\n . Ad\u2010Peli1 treatment attenuated cardiac fibrosis in Flk\u20101\n +\/\u2212<\/jats:sup>\n MI<\/jats:styled-content>\n mice. Similar positive results were observed in\n CD<\/jats:styled-content>\n 1 mice subjected to\n MI<\/jats:styled-content>\n after Ad\u2010Peli1 therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our results show for the first time that Peli1 plays a unique role in salvaging impaired collateral blood vessel formation, diminishes fibrosis, and improves myocardial function, thereby offering clinical potential for therapies in humans to mend a damaged heart following\n MI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.007601","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T15:02:17Z","timestamp":1537110137000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Disruption of VEGF Mediated Flk\u20101 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac\u00a0Function During Myocardial Infarction: Potential Therapy With Pellino\u20101"],"prefix":"10.1161","volume":"7","author":[{"given":"Mahesh","family":"Thirunavukkarasu","sequence":"first","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Department of Surgery University of Connecticut Health Farmington CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaithinathan","family":"Selvaraju","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Department of Surgery University of Connecticut Health Farmington CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandip","family":"Joshi","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Stanley J. Dudrick Department of Surgery Saint Mary's Hospital Waterbury CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Coca\u2010Soliz","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Stanley J. Dudrick Department of Surgery Saint Mary's Hospital Waterbury CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas","family":"Tapias","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Stanley J. Dudrick Department of Surgery Saint Mary's Hospital Waterbury CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"IbnalWalid","family":"Saad","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Stanley J. Dudrick Department of Surgery Saint Mary's Hospital Waterbury CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Fournier","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Department of Surgery University of Connecticut Health Farmington CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaftab","family":"Husain","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Department of Surgery University of Connecticut Health Farmington CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Campbell","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Angiogenesis Laboratory University of Connecticut Health Farmington CT"},{"name":"Department of Surgery University of Connecticut Health Farmington CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siu\u2010Pok","family":"Yee","sequence":"additional","affiliation":[{"name":"Center for Mouse Genome Modification University of Connecticut Health Farmington CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan A.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Stanley J. 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