{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:05:21Z","timestamp":1787497521771,"version":"build-2736575974"},"reference-count":15,"publisher":"BMJ","issue":"21","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2016,4,20]]},"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Coronary heart disease remains a significant clinical problem, and new therapies are needed especially for patients with refractory angina for whom the current therapies do not provide sufficient relief. The aim of this study was to find out if angiogenic gene therapy using new members of the vascular endothelial growth factor (VEGF) family, VEGF-B\n                      <jats:sub>186<\/jats:sub>\n                      and VEGF-D\n                      <jats:sup>\u0394N\u0394C<\/jats:sup>\n                      , increase myocardial perfusion as measured by the positron emission tomography (PET)\n                      <jats:sup>15<\/jats:sup>\n                      O-imaging, and whether there would be coronary steal effect to the contralateral side. Furthermore, safety of intramyocardial angiogenic adenoviral gene transfer was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Intramyocardial adenoviral (Ad) VEGF-B\n                      <jats:sub>186<\/jats:sub>\n                      or AdVEGF-D\n                      <jats:sup>\u0394N\u0394C<\/jats:sup>\n                      gene transfers were given endovascularly into the porcine posterolateral wall of the left ventricle (n=34). Six days later, PET\n                      <jats:sup>15<\/jats:sup>\n                      O-imaging for myocardial perfusion and coronary angiography were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AdVEGF-B\n                      <jats:sub>186<\/jats:sub>\n                      and AdVEGF-D\n                      <jats:sup>\u0394N\u0394C<\/jats:sup>\n                      induced angiogenesis and increased total microvascular area 1.8-fold (95% CI 0.2 to 3.5) and 2.8-fold (95% CI 1.4 to 4.3), respectively. At rest, perfusion was maintained at normal levels, but at stress, relative perfusion was increased 1.4-fold (95% CI 1.1 to 1.7) for AdVEGF-B\n                      <jats:sub>186<\/jats:sub>\n                      and 1.3-fold (95% CI 1.0 to 1.7) for AdVEGF-D\n                      <jats:sup>\u0394N\u0394C<\/jats:sup>\n                      , without causing coronary steal effect in the control area. The therapy was well tolerated and did not lead to any significant changes in laboratory safety parameters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Both AdVEGF-B\n                      <jats:sub>186<\/jats:sub>\n                      and AdVEGF-D\n                      <jats:sup>\u0394N\u0394C<\/jats:sup>\n                      gene transfers induced efficient angiogenesis in the myocardium resulting in an increased myocardial perfusion measured by PET. Importantly, local perfusion increase did not induce any coronary steal effect. As such, both treatments seem suitable new candidates for the induction of therapeutic angiogenesis for the treatment of refractory angina.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/heartjnl-2016-309373","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T22:49:36Z","timestamp":1463093376000},"page":"1716-1720","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["AdVEGF-B\n                    <sub>186<\/sub>\n                    and AdVEGF-D\n                    <sup>\u0394N\u0394C<\/sup>\n                    induce angiogenesis and increase perfusion in porcine myocardium"],"prefix":"10.1136","volume":"102","author":[{"given":"Jussi","family":"Nurro","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paavo J","family":"Halonen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Kuivanen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miikka","family":"Tarkia","sequence":"additional","affiliation":[{"name":"Turku PET Centre, Turku University Hospital, Turku, Finland"},{"name":"Department of Pharmacology, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Saraste","sequence":"additional","affiliation":[{"name":"Turku PET Centre, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Honkonen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"L\u00e4hteenvuo","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomas T","family":"Rissanen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"},{"name":"Department of Internal Medicine, Central Hospital of North Karelia, Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani","family":"Knuuti","sequence":"additional","affiliation":[{"name":"Turku PET Centre, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Yl\u00e4-Herttuala","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland"},{"name":"Science Service Center, Kuopio University Hospital, Kuopio, Finland"},{"name":"Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,5,12]]},"reference":[{"key":"2025092006030998000_102.21.1716.1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318282ab8f"},{"key":"2025092006030998000_102.21.1716.2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu299"},{"key":"2025092006030998000_102.21.1716.3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nrcardio.2013.200","article-title":"Treatment of refractory angina in patients not suitable for revascularization","volume":"11","author":"Henry","year":"2014","journal-title":"Nat Rev Cardiol"},{"key":"2025092006030998000_102.21.1716.4","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300175"},{"key":"2025092006030998000_102.21.1716.5","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000115519.03688.A2"},{"key":"2025092006030998000_102.21.1716.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.816454"},{"key":"2025092006030998000_102.21.1716.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.09.053"},{"key":"2025092006030998000_102.21.1716.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.12.068"},{"key":"2025092006030998000_102.21.1716.9","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.70"},{"key":"2025092006030998000_102.21.1716.10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.109.854893"},{"key":"2025092006030998000_102.21.1716.11","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.42.2.193"},{"key":"2025092006030998000_102.21.1716.12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.bbagen.2013.10.005","article-title":"The impact of the receptor binding profiles of the vascular endothelial growth factors on their angiogenic features","volume":"1840","author":"Nieminen","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"2025092006030998000_102.21.1716.13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00561.2013"},{"key":"2025092006030998000_102.21.1716.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2011.11.007"},{"key":"2025092006030998000_102.21.1716.15","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.543124"}],"container-title":["Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/heartjnl-2016-309373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T13:03:17Z","timestamp":1758373397000},"score":1,"resource":{"primary":{"URL":"https:\/\/heart.bmj.com\/lookup\/doi\/10.1136\/heartjnl-2016-309373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,12]]},"references-count":15,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2016,10,12]]},"published-print":{"date-parts":[[2016,11,1]]}},"alternative-id":["10.1136\/heartjnl-2016-309373"],"URL":"https:\/\/doi.org\/10.1136\/heartjnl-2016-309373","relation":{},"ISSN":["1355-6037","1468-201X"],"issn-type":[{"value":"1355-6037","type":"print"},{"value":"1468-201X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,12]]}}}