{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:49:06Z","timestamp":1789469346304,"version":"build-2803163510"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"4","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32HL007260"],"award-info":[{"award-number":["T32HL007260"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F30HL129629"],"award-info":[{"award-number":["F30HL129629"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006812","name":"Center for Integrated Healthcare, U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX002327"],"award-info":[{"award-number":["BX002327"]}],"id":[{"id":"10.13039\/100006812","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,22]]},"abstract":"<jats:p>Myocardial infarctions (MIs) cause the loss of myocytes due to lack of sufficient oxygenation and latent revascularization. Although the administration of histone deacetylase (HDAC) inhibitors reduces the size of infarctions and improves cardiac physiology in small-animal models of MI injury, the cellular targets of the HDACs, which the drugs inhibit, are largely unspecified. Here, we show that WNT-inducible secreted protein-1 (Wisp-1), a matricellular protein that promotes angiogenesis in cancers as well as cell survival in isolated cardiac myocytes and neurons, is a target of HDACs. Further, Wisp-1 transcription is regulated by HDACs and can be modified by the HDAC inhibitor, suberanilohydroxamic acid (SAHA\/vorinostat), after MI injury. We observe that, at 7 days after MI, Wisp-1 is elevated 3-fold greater in the border zone of infarction in mice that experience an MI injury and are injected daily with SAHA, relative to MI alone. Additionally, human coronary artery endothelial cells (HCAECs) produce WISP-1 and are responsive to autocrine WISP-1\u2013mediated signaling, which functionally promotes their proangiogenic behavior. Altering endogenous expression of WISP-1 in HCAECs directly impacts their network density in vitro. Therapeutic interventions after a heart attack define the extent of infarct injury, cell survival, and overall prognosis. Our studies shown here identify a potentially novel cardiac angiokine, Wisp-1, that may contribute to beneficial post-MI treatment modalities.<\/jats:p>","DOI":"10.1172\/jci.insight.95824","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T11:00:58Z","timestamp":1519210858000},"source":"Crossref","is-referenced-by-count":26,"title":["Angiokine Wisp-1 is increased in myocardial infarction and regulates cardiac endothelial signaling"],"prefix":"10.1172","volume":"3","author":[{"given":"Lillianne H.","family":"Wright","sequence":"first","affiliation":[{"name":"Division of Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Herr","sequence":"additional","affiliation":[{"name":"Division of Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Symone S.","family":"Brown","sequence":"additional","affiliation":[{"name":"College of Graduate Studies, Summer Undergraduate Research Program, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harinath","family":"Kasiganesan","sequence":"additional","affiliation":[{"name":"Division of Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald R.","family":"Menick","sequence":"additional","affiliation":[{"name":"Division of Cardiology, and"},{"name":"Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000152"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4849"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119656"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000053618.86362.DF"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000085658.98621.49"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.74.4.693"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4155\/tde.12.50"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306146"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004708107"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00008.2011"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-005-0026-0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00428.2007"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.07.025"},{"issue":"6","key":"B14","doi-asserted-by":"crossref","first-page":"4239","DOI":"10.18632\/oncotarget.2978","article-title":"WISP-1 a novel angiogenic regulator of the CCN family promotes oral squamous cell carcinoma angiogenesis through VEGF-A expression","volume":"6","author":"Chuang","year":"2015","journal-title":"Oncotarget"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14717"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.07.012"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/156720213804805945"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.04.172"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015081108"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-21631-2_4"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(199608)62:2<149::AID-JCB2>3.0.CO;2-S"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1139\/o01-032"},{"key":"B23","first-page":"53","article-title":"Transcription Regulation by Class III Histone Deacetylases (HDACs)-Sirtuins","volume":"3","author":"Dai","year":"2008","journal-title":"Transl Oncogenomics"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.03.005"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-108548"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.08.010"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00891.2006"},{"issue":"5","key":"B28","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1101\/gad.14.5.585","article-title":"WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene","volume":"14","author":"Xu","year":"2000","journal-title":"Genes Dev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.8.3404-3414.2004"},{"issue":"52","key":"B30","doi-asserted-by":"crossref","DOI":"10.3791\/2581","article-title":"Coronary artery ligation and intramyocardial injection in a murine model of infarction","author":"Virag","year":"2011","journal-title":"J Vis Exp"},{"issue":"6","key":"B31","first-page":"125","article-title":"[Modeling of myocardial pathology in mice with the surgical methods]","volume":"17","author":"Kogan","year":"1977","journal-title":"Kardiologiia"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002416"},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.1186\/s12933-015-0262-8","article-title":"Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice","volume":"14","author":"Chen","year":"2015","journal-title":"Cardiovasc Diabetol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1496"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00429-4"},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/641979","article-title":"Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases","volume":"2014","author":"Wang","year":"2014","journal-title":"Oxid Med Cell Longev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2174\/156720212800410858"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.8.1839"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-13"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.055541"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2009.07.010"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01210.2003"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-007-9376-x"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108339200"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-145102"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-096438"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1322"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81382-3"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203076"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.2174\/156720212803530618"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.2174\/156720212799297137"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.20185"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015081108"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.008115"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0445-4"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1936213100"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307626"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.11.008"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303922"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.628818"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00479.2005"},{"key":"B62","first-page":"20","article-title":"Cardioprotection by estrogens: implications of observational studies","volume":"39 Suppl 1","author":"Samsioe","year":"1994","journal-title":"Int J Fertil Menopausal Stud"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.307509"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0756.2011.01631.x"},{"issue":"24","key":"B65","first-page":"8917","article-title":"Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features","volume":"61","author":"Xie","year":"2001","journal-title":"Cancer Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.06.011"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.62.2.212"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1251\/bpo31"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5860"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809757200"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/95824\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:03:26Z","timestamp":1779195806000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/95824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,22]]},"references-count":70,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,2,22]]},"published-print":{"date-parts":[[2018,2,22]]}},"alternative-id":["10.1172\/jci.insight.95824"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.95824","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,22]]},"article-number":"e95824"}}