{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:13:08Z","timestamp":1792793588653,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,11,27]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>MicroRNAs (miRs) regulate nearly all biological pathways. Because the dysregulation of miRs can lead to disease progression, they are being explored as novel therapeutic targets. However, the cell type-specific effects of miRs in the heart are poorly understood. Thus, we assessed miR target regulation using miR-92a-3p as an example. Inhibition of miR-92a is known to improve endothelial cell function and recovery after acute myocardial infarction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              miR-92a-3p was inhibited by locked nucleic acid (LNA)-based antimiR (LNA-92a) in mice after myocardial infarction. Expression of regulated genes was evaluated 3 days after myocardial infarction by RNA sequencing of isolated endothelial cells, cardiomyocytes, fibroblasts, and CD45\n              <jats:sup>+<\/jats:sup>\n              hematopoietic cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>LNA-92a depleted miR-92a-3p expression in all cell types and derepressed predicted miR-92a-3p targets in a cell type-specific manner. RNAseq showed endothelial cell-specific regulation of autophagy-related genes. Imaging confirmed increased endothelial cell autophagy in LNA-92a treated relative to control animals. In vitro inhibition of miR-92a-3p augmented EC autophagy, derepressed autophagy-related gene 4a, and increased luciferase activity in autophagy-related gene 4a 3\u2019UTR containing reporters, whereas miR-92a-3p overexpression had the opposite effect. In cardiomyocytes, LNA-92a derepressed metabolism-related genes, notably, the high-density lipoprotein transporter Abca8b. LNA-92a further increased fatty acid uptake and mitochondrial function in cardiomyocytes in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our data show that miRs have cell type-specific effects in vivo. Analysis of miR targets in cell subsets disclosed a novel function of miR-92a-3p in endothelial cell autophagy and cardiomyocyte metabolism. Because autophagy is upregulated during ischemia to supply nutrients and cardiomyocyte metabolic-switching improves available substrate utilization, these prosurvival mechanisms may diminish tissue damage.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.034598","type":"journal-article","created":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T17:35:43Z","timestamp":1546882543000},"page":"2545-2558","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":79,"title":["Analysis of Cell Type-Specific Effects of MicroRNA-92a Provides Novel Insights Into Target Regulation and Mechanism of Action"],"prefix":"10.1161","volume":"138","author":[{"given":"Eva-Maria","family":"Rogg","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., S.D.)."},{"name":"German Centre of Cardiovascular Research, RheinMain (E.-M.R., W.T.A., M.H.S., A.B., A.M.Z., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley T.","family":"Abplanalp","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., S.D.)."},{"name":"German Centre of Cardiovascular Research, RheinMain (E.-M.R., W.T.A., M.H.S., A.B., A.M.Z., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Bischof","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"John","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel H.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., S.D.)."},{"name":"German Centre of Cardiovascular Research, RheinMain (E.-M.R., W.T.A., M.H.S., A.B., A.M.Z., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University, Frankfurt, Germany (E.-M.R., W.T.A., C.B., D.J., M.H.S., J.K., A.F., A.B., 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