{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:44:34Z","timestamp":1783820674576,"version":"3.55.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,10,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>BACKGROUND<\/jats:title>\n            <jats:p xml:lang=\"en\">New pharmacological approaches are needed to prevent stent restenosis. This study tested the hypothesis that pemafibrate, a novel clinical selective PPAR\u03b1 (peroxisome proliferator\u2010activated receptor \u03b1) agonist, suppresses coronary stent\u2010induced arterial inflammation and neointimal hyperplasia.<\/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              Yorkshire pigs randomly received either oral pemafibrate (30\u00a0mg\/day; n=6) or control vehicle (n=7) for 7\u00a0days, followed by coronary arterial implantation of 3.5\u00a0\u00d7\u00a012\u00a0mm bare metal stents (2\u20134 per animal; 44 stents total). On day 7, intracoronary molecular\u2010structural near\u2010infrared fluorescence and optical coherence tomography imaging was performed to assess the arterial inflammatory response, demonstrating that pemafibrate reduced stent\u2010induced inflammatory protease activity (near\u2010infrared fluorescence target\u2010to\u2010background ratio: pemafibrate, median [25th\u201075th percentile]: 2.8 [2.5\u20133.3] versus control, 4.1 [3.3\u20134.3],\n              <jats:italic>P<\/jats:italic>\n              =0.02). At day 28, animals underwent repeat near\u2010infrared fluorescence\u2013optical coherence tomography imaging and were euthanized, and coronary stent tissue molecular and histological analyses. Day 28 optical coherence tomography imaging showed that pemafibrate significantly reduced stent neointima volume (pemafibrate, 43.1 [33.7\u201354.1] mm\n              <jats:sup>3<\/jats:sup>\n              versus control, 54.2 [41.2\u201381.1] mm\n              <jats:sup>3<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.03). In addition, pemafibrate suppressed day 28 stent\u2010induced cellular inflammation and neointima expression of the inflammatory mediators TNF\u2010\u03b1 (tumor necrosis factor\u2010\u03b1) and MMP\u20109 (matrix metalloproteinase 9) and enhanced the smooth muscle differentiation markers calponin and smoothelin. In vitro assays indicated that the STAT3 (signal transducer and activator of transcription 3)\u2013myocardin axes mediated the inhibitory effects of pemafibrate on smooth muscle cell proliferation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>CONCLUSIONS<\/jats:title>\n            <jats:p xml:lang=\"en\">Pemafibrate reduces preclinical coronary stent inflammation and neointimal hyperplasia following bare metal stent deployment. These results motivate further trials evaluating pemafibrate as a new strategy to prevent clinical stent restenosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.020834","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T09:21:49Z","timestamp":1633944109000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Highly Selective PPAR\u03b1 (Peroxisome Proliferator\u2010Activated Receptor \u03b1) Agonist Pemafibrate Inhibits Stent Inflammation and Restenosis Assessed by Multimodality Molecular\u2010Microstructural Imaging"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7098-9406","authenticated-orcid":false,"given":"Hiroshi","family":"Iwata","sequence":"first","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"},{"name":"Department of Cardiovascular Biology and Medicine Juntendo University Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-8470","authenticated-orcid":false,"given":"Eric A.","family":"Osborn","sequence":"additional","affiliation":[{"name":"Cardiovascular Research CenterCardiology DivisionMassachusetts General HospitalHarvard Medical School Boston MA"},{"name":"Cardiology Division Beth Israel Deaconess Medical CenterHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni J.","family":"Ughi","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Murakami","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Goettsch","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8383-4435","authenticated-orcid":false,"given":"Joshua D.","family":"Hutcheson","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Mauskapf","sequence":"additional","affiliation":[{"name":"Cardiovascular Research CenterCardiology DivisionMassachusetts General HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Mattson","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-502X","authenticated-orcid":false,"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha A.","family":"Singh","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-9269","authenticated-orcid":false,"given":"Joan","family":"Matamalas","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7835-2135","authenticated-orcid":false,"given":"Elena","family":"Aikawa","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"},{"name":"Center for Excellence in Vascular Biology Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"},{"name":"Department of Human Pathology I.M. Sechenov First Moscow State Medical University of the Ministry of Health Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo J.","family":"Tearney","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General HospitalHarvard Medical School Boston MA"},{"name":"Department of Pathology Massachusetts General HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-2079","authenticated-orcid":false,"given":"Masanori","family":"Aikawa","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"},{"name":"Center for Excellence in Vascular Biology Cardiovascular Division Brigham and Women\u2019s Hospital Harvard Medical School Boston MA"},{"name":"Channing Division of Network Medicine Brigham and Women\u2019s HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7980-384X","authenticated-orcid":false,"given":"Farouc A.","family":"Jaffer","sequence":"additional","affiliation":[{"name":"Cardiovascular Research CenterCardiology DivisionMassachusetts General HospitalHarvard Medical School Boston MA"},{"name":"Wellman Center for Photomedicine Massachusetts General HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu383"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.118.007023"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4244\/EIJV14I12A226"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.01.011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2014.948844"},{"key":"e_1_3_2_7_2","first-page":"III47","article-title":"A cascade model for restenosis. 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