{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:56:32Z","timestamp":1790427392457,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,6,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Mesenchymal stem cell\u2013derived extracellular vesicles (\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell\u2013derived\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Twenty\u2010three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (\n              <jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>\n              ; n=7) and the\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              myocardial injection group (\n              <jats:styled-content style=\"fixed-case\">MVM<\/jats:styled-content>\n              ; n=10). The\n              <jats:styled-content style=\"fixed-case\">MVM<\/jats:styled-content>\n              group underwent myocardial injection of 50\u00a0\u03bcg of\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s in 2\u00a0mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic\/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the\n              <jats:styled-content style=\"fixed-case\">MVM<\/jats:styled-content>\n              group compared with the\n              <jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>\n              group. Pigs in the\n              <jats:styled-content style=\"fixed-case\">MVM<\/jats:styled-content>\n              group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with\n              <jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>\n              pigs. There was an increase in expression of the phospho\u2013mitogen\u2010activated protein kinase\/mitogen\u2010activated protein kinase ratio, the phospho\u2013endothelial nitric oxide synthase\/endothelial nitric oxide synthase ratio, and total protein kinase B in the\n              <jats:styled-content style=\"fixed-case\">MVM<\/jats:styled-content>\n              group compared with\n              <jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>\n              . There was an increase in cardiac output and stroke volume in the\n              <jats:styled-content style=\"fixed-case\">MVM<\/jats:styled-content>\n              group compared with CON.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell\u2013derived\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B\/endothelial nitric oxide synthase and mitogen\u2010activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.008344","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T09:15:24Z","timestamp":1528794924000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia"],"prefix":"10.1161","volume":"7","author":[{"given":"Brittany A.","family":"Potz","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Scrimgeour","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasile I.","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neel R.","family":"Sodha","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Ruhul","family":"Abid","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Sellke","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","first-page":"503","article-title":"Involvement of endoplasmic reticulum stress\u2010associated apoptosis in a heart failure model induced by chronic myocardial ischemia","volume":"27","author":"Xin W","year":"2011","unstructured":"Xin W, Li X, Lu X, Niu K, Cai J. 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