{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:09:19Z","timestamp":1791205759659,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,1,5]]},"abstract":"\n Background<\/jats:title>\n \n Dilated cardiomyopathy is characterized by impaired contractility of cardiomyocytes, ventricular chamber dilatation, and systolic dysfunction. Although mutations in genes expressed in the cardiomyocyte are the best described causes of reduced contractility, the importance of endothelial\u2010cardiomyocyte communication for proper cardiac function is increasingly appreciated. In the present study, we investigate the role of the endothelial adhesion molecule platelet endothelial cell adhesion molecule (\n PECAM<\/jats:styled-content>\n \u20101) in the regulation of cardiac function.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Using cell culture and animal models\n ,<\/jats:italic>\n we show that\n PECAM<\/jats:styled-content>\n \u20101 expressed in endothelial cells (\n EC<\/jats:styled-content>\n s) regulates cardiomyocyte contractility and cardiac function via the neuregulin\u2010ErbB signaling pathway. Conscious echocardiography revealed left ventricular (\n LV<\/jats:styled-content>\n ) chamber dilation and systolic dysfunction in\n PECAM<\/jats:styled-content>\n \u20101\n \u2212\/\u2212<\/jats:sup>\n mice in the absence of histological abnormalities or defects in cardiac capillary density. Despite deficits in global cardiac function, cardiomyocytes isolated from\n PECAM<\/jats:styled-content>\n \u20101\n \u2212\/\u2212<\/jats:sup>\n hearts displayed normal baseline and isoproterenol\u2010stimulated contractility. Mechanistically, absence of\n PECAM<\/jats:styled-content>\n \u20101 resulted in elevated\n NO<\/jats:styled-content>\n \/\n ROS<\/jats:styled-content>\n signaling and\n NRG<\/jats:styled-content>\n \u20101 release from\n EC<\/jats:styled-content>\n s, which resulted in augmented phosphorylation of its receptor ErbB2. Treatment of cardiomyocytes with conditioned media from\n PECAM<\/jats:styled-content>\n \u20101\n \u2212\/\u2212<\/jats:sup>\n EC<\/jats:styled-content>\n s resulted in enhanced ErbB2 activation, which was normalized by pre\u2010treatment with an\n NRG<\/jats:styled-content>\n \u20101 blocking antibody. To determine whether normalization of increased\n NRG<\/jats:styled-content>\n \u20101 levels could correct cardiac function,\n PECAM<\/jats:styled-content>\n \u20101\n \u2212\/\u2212<\/jats:sup>\n mice were treated with the\n NRG<\/jats:styled-content>\n \u20101 blocking antibody. Echocardiography showed that treatment significantly improved cardiac function of\n PECAM<\/jats:styled-content>\n \u20101\n \u2212\/\u2212<\/jats:sup>\n mice, as revealed by increased ejection fraction and fractional shortening.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We identify a novel role for\n PECAM<\/jats:styled-content>\n \u20101 in regulating cardiac function via a paracrine\n NRG<\/jats:styled-content>\n 1\u2010ErbB pathway. These data highlight the importance of tightly regulated cellular communication for proper cardiac function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.001210","type":"journal-article","created":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T02:59:21Z","timestamp":1421722761000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Platelet Endothelial Cell Adhesion Molecule\u20101 Mediates Endothelial\u2010Cardiomyocyte Communication and Regulates Cardiac Function"],"prefix":"10.1161","volume":"4","author":[{"given":"Margaret E.","family":"McCormick","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina 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