{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:12:38Z","timestamp":1790827958511,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Imaging"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Rapid screening and accurate diagnosis of acute myocardial infarction are critical to reduce the progression of myocardial necrosis, in which proteolytic degradation of myocardial extracellular matrix plays a major role. In previous studies, we found that targeting the extracellular matrix metalloprotease inducer (EMMPRIN) by injecting nanoparticles conjugated with the specific EMMPRIN-binding peptide AP9 significantly improved cardiac function in mice subjected to ischemia\/reperfusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In a porcine model of coronary ischemia\/reperfusion, we tested the theragnostic effects of administering 0.1 mg\/kg gadolinium-containing nanoparticles conjugated with AP9 (NAP9), a synthetic peptide that targets EMMPRIN or a control nanoparticle (NAPSC). Cardiac magnetic resonance assessment of the infarct progression, ventricular function, and nanoparticle distribution was performed the next 7 days. We also measured the infarcted area of the heart and cardiac remodeling at 7 or 21 days after ischemia\/reperfusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>After 21 days of ischemia\/reperfusion, NAP9 reduced the extension of cardiac necrosis (14.1\u00b19.7 versus 35.5\u00b11.8) and the levels of collagenolytic activity of MMPs (matrix metalloproteases), along with a significant reduction in collagen deposition (7.5\u00b14.5 versus 41.3\u00b120); including the ratio of type I versus III collagen fibers in the necrotic myocardium. In terms of cardiac function, the response to NAP9 administration resulted in a significant improvement of cardiac performance overtime, as evidenced by the left ventricle ejection fraction (64.0\u00b17.8), when compared with those present in the NAPSC group (47.3\u00b14.7). As shown by magnetic resonance imaging, noninvasive molecular imaging of NAP9 enabled us to find a significant reduction in cardiac necrosis, myocardial edema, hemorrhage, and microvascular obstruction, suggesting that NAP9 may reduce myocardial injury and preserve left ventricular function, at least, by preventing the effect of EMMPRIN on extracellular matrix degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our data point towards NAP9 as a promising theragnostic tool in managing acute myocardial infarction, by inhibiting EMMPRIN-induced extracellular matrix degradation and allowing noninvasive visualization of cardiac necrosis progression over time.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circimaging.121.013379","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T05:00:38Z","timestamp":1654750838000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Theranostic Contribution of Extracellular Matrix Metalloprotease Inducer-Paramagnetic Nanoparticles Against Acute Myocardial Infarction in a Pig Model of Coronary Ischemia-Reperfusion"],"prefix":"10.1161","volume":"15","author":[{"given":"Rafael","family":"Ramirez-Carracedo","sequence":"first","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cardiovascular, Departamento de Cardiolog\u00eda, Universidad Francisco de Vitoria, Hospital Ram\u00f3n y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-4579","authenticated-orcid":true,"given":"Marcelo","family":"Sanmartin","sequence":"additional","affiliation":[{"name":"Departamento de Cardiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal (IRYCIS), Madrid, Spain (M. Sanmartin, J.L.Z.)."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-7767","authenticated-orcid":true,"given":"Amadeo","family":"Ten","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n de salud La Fe, Grupo de Investigaci\u00f3n Biom\u00e9dica (GIBI230-PREBI). Nodo de Imagen La Fe en la Red de Imagen Biom\u00e9dica (ReDIB) de Infraestructuras Cient\u00edficas T\u00e9cnicas y Singulares (ICTS), Valencia, Spain (A.T., L.M.-B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-534X","authenticated-orcid":true,"given":"Ignacio","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cardiovascular, Departamento de Cardiolog\u00eda, Universidad Francisco de Vitoria, Hospital Ram\u00f3n y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tesoro","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cardiovascular, Departamento de Cardiolog\u00eda, Universidad Francisco de Vitoria, Hospital Ram\u00f3n y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Diez-Mata","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cardiovascular, Departamento de Cardiolog\u00eda, Universidad Francisco de Vitoria, Hospital Ram\u00f3n y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-9880","authenticated-orcid":true,"given":"Laura","family":"Botana","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cardiovascular, Departamento de Cardiolog\u00eda, Universidad Francisco de Vitoria, Hospital Ram\u00f3n y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Ovejero-Paredes","sequence":"additional","affiliation":[{"name":"Grupo de Nanobiotecnolog\u00eda para Ciencias de la Vida, Departamento de Qu\u00edmica en Ciencias Farmaceuticas Facultad de Farmacia, Universidad Complutense de Madrid (UCM). Unidad de Microscopia e Imagen Dinamica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (K.O.-P., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Filice","sequence":"additional","affiliation":[{"name":"QUIBIM SL \u2013 Quantitative Imaging Biomarkers in Medicine, Valencia, Spain (A.A.-B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-2392","authenticated-orcid":true,"given":"Angel","family":"Alberich-Bayarri","sequence":"additional","affiliation":[{"name":"Departamento de Cirug\u00eda Experimental, Hospital Universitario La Paz, Madrid, Spain (C.L.-A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-010X","authenticated-orcid":true,"given":"Luis","family":"Mart\u00ed-Bonmat\u00ed","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n de salud La Fe, Grupo de Investigaci\u00f3n Biom\u00e9dica (GIBI230-PREBI). 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