{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:06:54Z","timestamp":1790651214155,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>MicroRNAs are small, noncoding RNAs that play a key role in gene expression. Accumulating evidence suggests that aberrant microRNA expression contributes to the heart failure (HF) phenotype; however, the underlying molecular mechanisms are not well understood. A better understanding of the mechanisms of action of microRNAs could potentially lead to targeted therapies that could halt the progression or even reverse HF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              We found that microRNA-152 (miR-152) expression was upregulated in the failing human heart and experimental animal models of HF. Transgenic mice with cardiomyocyte-specific miR-152 overexpression developed systolic dysfunction (mean difference, \u221238.74% [95% CI, \u221245.73% to \u221231.74%];\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and dilated cardiomyopathy. At the cellular level, miR-152 overexpression perturbed mitochondrial ultrastructure and dysregulated key genes involved in cardiomyocyte metabolism and inflammation. Mechanistically, we identified Glrx5 (glutaredoxin 5), a critical regulator of mitochondrial iron homeostasis and iron-sulfur cluster synthesis, as a direct miR-152 target. Finally, a proof-of-concept of the therapeutic efficacy of targeting miR-152 in vivo was obtained by utilizing a locked nucleic acid\u2013based inhibitor of miR-152 (LNA 152) in a murine model of HF subjected to transverse aortic constriction. We demonstrated that animals treated with LNA\u2013152 (n=10) showed preservation of systolic function when compared with locked nucleic acid\u2013control treated animals (n=9; mean difference, 18.25% [95% CI, 25.10% to 11.39%];\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The upregulation of miR-152 expression in the failing myocardium contributes to HF pathophysiology. Preclinical evidence suggests that miR-152 inhibition preserves cardiac function in a model of pressure overload\u2013induced HF. These findings offer new insights into the pathophysiology of HF and point to miR-152-Glrx5 axis as a potential novel therapeutic target.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.119.006298","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T09:00:23Z","timestamp":1584003623000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Pharmacological Silencing of MicroRNA-152 Prevents Pressure Overload\u2013Induced Heart Failure"],"prefix":"10.1161","volume":"13","author":[{"given":"Thomas J.","family":"LaRocca","sequence":"first","affiliation":[{"name":"Division of Critical Care Medicine, Department of Pediatrics, Lucile Packard Children\u2019s Hospital (T.J.L.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Seeger","sequence":"additional","affiliation":[{"name":"Stanford 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CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigham H.","family":"Mecham","sequence":"additional","affiliation":[{"name":"Trialomics, LLC, Seattle, WA (B.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ameen","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute (T.S., I.P.-G., E.N., M.A., J.C.W., I.K.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Chia Yu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Shanghai Institute of Precision Medicine, Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, China (A.C.Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn 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