{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:54:44Z","timestamp":1791302084235,"version":"4.1.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,1,6]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>\/\u2212<\/jats:sup>\n              and\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              , we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II\u2013infused\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in\n              <jats:italic>Timp3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of atherosclerosis and aneurysms and protecting them from rupture.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.309321","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T03:44:32Z","timestamp":1476848672000},"page":"49-65","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":154,"title":["MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin"],"prefix":"10.1161","volume":"120","author":[{"given":"Karina","family":"Di Gregoli","sequence":"first","affiliation":[{"name":"From the Laboratory of Cardiovascular Pathology, School of Clinical Sciences, University of Bristol, England."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Najmi","family":"Mohamad Anuar","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cardiovascular Pathology, School of Clinical Sciences, University of Bristol, 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