{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:36:42Z","timestamp":1791491802472,"version":"4.3.4"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T00:00:00Z","timestamp":1681516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NIH","doi-asserted-by":"publisher","award":["R01HL073646"],"award-info":[{"award-number":["R01HL073646"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic\/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathways to limit myocardial IRI. Perfluorocarbon nanoparticles (PFC NP) were covalently coupled with an irreversible thrombin inhibitor, PPACK (Phe[D]-Pro-Arg-Chloromethylketone), and delivered intravenously to animals in a single dose prior to ischemia reperfusion injury. Fluorescent microscopy of tissue sections and 19F magnetic resonance images of whole hearts ex vivo demonstrated abundant delivery of PFC NP to the area at risk. Echocardiography at 24 h after reperfusion demonstrated preserved ventricular structure and improved function. Treatment reduced thrombin deposition, suppressed endothelial activation, inhibited inflammasome signaling pathways, and limited microvascular injury and vascular pruning in infarct border zones. Accordingly, thrombin inhibition with an extraordinarily potent but locally acting agent suggested a critical role for thrombin and a promising therapeutic strategy in cardiac IRI.<\/jats:p>","DOI":"10.3390\/ijms24087333","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T03:14:09Z","timestamp":1681701249000},"page":"7333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0654-9022","authenticated-orcid":false,"given":"Ian","family":"Vargas","sequence":"first","affiliation":[{"name":"University of South Florida Heart Institute, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Grabau","sequence":"additional","affiliation":[{"name":"University of South Florida Heart Institute, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Consortium for Translational Research in Advanced Imaging and Nanomedicine, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Weinheimer","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Dominguez-Viqueira","sequence":"additional","affiliation":[{"name":"Small Animal Imaging Laboratory, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Wickline","sequence":"additional","affiliation":[{"name":"University of South Florida Heart Institute, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA"},{"name":"Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/CIRCRESAHA.112.300627","article-title":"Current state of clinical translation of cardioprotective agents for acute myocardial infarction","volume":"113","author":"Kloner","year":"2013","journal-title":"Circ. 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