{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:38:26Z","timestamp":1789436306926,"version":"build-2803163510"},"reference-count":87,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,10,10]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Mechanisms of macrophage switching from proinflammatory to anti-inflammatory phenotypes are not well understood. Circular RNAs, a new class of noncoding RNAs, are implicated in immune modulation. We recently identified circ-cdr1as as a regulator of macrophage phenotype in bone marrow-derived macrophages; however, its role in immunomodulation during cardiovascular injury remains unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Cell-specific expression levels of circ-cdr1as were determined in the mouse hearts postmyocardial infarction. Circ-cdr1as was overexpressed in fluorescently labeled bone marrow-derived macrophages and injected into the ischemic myocardium immediately following myocardial infarction. The effect of AAV9 (adeno-associated virus-serotype 9)-mediated systemic delivery of circ-Cdr1as on postmyocardial infarction cardiac function and structure was determined. Downstream mechanisms were studied using gain and loss-of-function strategies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>Cardiac cell-specific expression analysis showed significant downregulation of circ-cdr1as only in macrophages and cardiomyocytes. Overexpression of circ-cdr1as in bone marrow-derived macrophages, injected into the ischemic myocardium, retained their anti-inflammatory phenotype and significantly improved left ventricular functions and reduced infarct size. Systemic delivery of AAV9-circ-cdr1as showed similar cardiac reparative activity. Mechanistically, circ-cdr1as directly binds and sponges microRNA-7 and increases the expression of target KLF4 (Kruppel-like factor 4). Loss and gain of function studies show that modulation of microRNA 7 and KLF recapitulates macrophage phenotypic changes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Circ-cdr1as plays a crucial role in regulating the anti-inflammatory phenotype of macrophages through modulation of microRNA 7 and its target gene KLF4. Therefore, circ-cdr1as holds potential as an anti-inflammatory regulator in tissue inflammation postcardiac injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.125.326377","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T09:00:14Z","timestamp":1758013214000},"page":"1207-1221","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Circular RNA Cdr1as Modulates Macrophage-Mediated Cardiac Reparative Function"],"prefix":"10.1161","volume":"137","author":[{"given":"Carolina","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Aging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cimini","sequence":"additional","affiliation":[{"name":"Aging and 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