{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:49:09Z","timestamp":1789732149347,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T00:00:00Z","timestamp":1489363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2017,4]]},"abstract":"Summary<\/jats:title>Introduction<\/jats:title>Rap1, a member of Ras superfamily of small GTP<\/jats:styled-content>\u2010binding proteins, is involved in cardiovascular biology in numerous ways. It is an evolutionary conserved regulator of adhesion, polarity, differentiation and growth.<\/jats:p><\/jats:sec>Aims<\/jats:title>Our aim was to analyze Rap1\u2010activated rat bone marrow mesenchymal stem cells (MSC<\/jats:styled-content>s) for their potential role in adhesion and cardiac differentiation.<\/jats:p><\/jats:sec>Methods<\/jats:title>Myocardial infarction (MI<\/jats:styled-content>) was produced in Sprague Dawley (SD<\/jats:styled-content>) rats through occlusion of the left anterior descending coronary artery. MSC<\/jats:styled-content>s were treated with 8\u2010pCPT<\/jats:styled-content>\u20102\u2032\u2010O\u2010Me\u2010cAMP<\/jats:styled-content> (CPT<\/jats:styled-content>) to activate Rap1. Normal (untreated) and CPT<\/jats:styled-content>\u2010treated MSC<\/jats:styled-content>s were transplanted through intramyocardial injection in respective groups. Cardiac function was assessed by echocardiography at 2 and 4\u00a0weeks after cell transplantation. Histological analysis was performed to observe changes at tissue level.<\/jats:p><\/jats:sec>Results<\/jats:title>Homing of CPT<\/jats:styled-content>\u2010treated MSC<\/jats:styled-content>s was significantly (***P<\/jats:italic><.001) higher as compared to normal MSC<\/jats:styled-content>s in the infarcted hearts. This may be due to increase in the gene expression of some of the cell adhesion molecules as evident by qRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content> analysis. Significant (***P<\/jats:italic><.001) improvement in the restoration of heart function in terms of left ventricular diastolic and systolic internal diameters (LVID<\/jats:styled-content>d, LVID<\/jats:styled-content>s), % ejection fraction, % fraction shortening and end\u2010systolic and end\u2010diastolic volumes were observed in CPT<\/jats:styled-content>\u2010treated MSC<\/jats:styled-content>s as compared to the MI<\/jats:styled-content> model. Histological analyses showed significant (***P<\/jats:italic><.001) reduction in scar formation in the CPT<\/jats:styled-content>\u2010treated group. Differentiation of treated MSC<\/jats:styled-content>s into functional cardiomyocytes was evident through immunohistochemical staining. LV<\/jats:styled-content> wall thickness was also preserved significantly (***P<\/jats:italic><.001). Blood vessel formation was more pronounced in CPT<\/jats:styled-content>\u2010treated group although both cell therapy groups showed significant increase as compared to MI<\/jats:styled-content> model.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings showed that pharmacological activation of Epac\u2010Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSC<\/jats:styled-content>s in the infarct area restored functional myocardium.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12248","type":"journal-article","created":{"date-parts":[[2016,12,31]],"date-time":"2016-12-31T10:56:36Z","timestamp":1483181796000},"source":"Crossref","is-referenced-by-count":32,"title":["Epac\u2010Rap1\u2010activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction"],"prefix":"10.1111","volume":"35","author":[{"given":"Irfan","family":"Khan","sequence":"first","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological Sciences University of Karachi Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar","family":"Ali","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological Sciences 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