{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T20:06:35Z","timestamp":1785355595986,"version":"3.55.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,8,17]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>MicroRNA-499 and other members of the myomiR family regulate myosin isoforms in pressure-overload hypertrophy. miR-499 expression varies in human disease, but results of mouse cardiac miR-499 overexpression are inconsistent, either protecting against ischemic damage or aggravating cardiomyopathy after pressure overload. Likewise, there is disagreement over direct and indirect cardiac mRNAs targeted in vivo by miR-499.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To define the associations between regulated miR-499 level in clinical and experimental heart disease and modulation of its predicted mRNA targets and to determine the consequences of increased cardiac miR-499 on direct mRNA targeting, indirect mRNA modulation, and on myocardial protein content and posttranslational modification.<\/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>miR-499 levels were increased in failing and hypertrophied human hearts and associated with decreased levels of predicted target mRNAs. Likewise, miR-499 is increased in Gq-mediated murine cardiomyopathy. Forced cardiomyocyte expression of miR-499 at levels comparable to human cardiomyopathy induced progressive murine heart failure and exacerbated cardiac remodeling after pressure overloading. Genome-wide RNA-induced silencing complex and RNA sequencing identified 67 direct, and numerous indirect, cardiac mRNA targets, including Akt and MAPKs. Myocardial proteomics identified alterations in protein phosphorylation linked to the miR-499 cardiomyopathy phenotype, including of heat shock protein 90 and protein serine\/threonine phosphatase 1-\u03b1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>miR-499 is increased in human and murine cardiac hypertrophy and cardiomyopathy, is sufficient to cause murine heart failure, and accelerates maladaptation to pressure overloading. The deleterious effects of miR-499 reflect the cumulative consequences of direct and indirect mRNA regulation, modulation of cardiac kinase and phosphatase pathways, and higher-order effects on posttranslational modification of myocardial proteins.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.265736","type":"journal-article","created":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:34:41Z","timestamp":1341102881000},"page":"521-531","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":130,"title":["Direct and Indirect Involvement of MicroRNA-499 in Clinical and Experimental Cardiomyopathy"],"prefix":"10.1161","volume":"111","author":[{"given":"Scot J.","family":"Matkovich","sequence":"first","affiliation":[{"name":"From the Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Eschenbacher","sequence":"additional","affiliation":[{"name":"From the Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa E.","family":"Dorn","sequence":"additional","affiliation":[{"name":"From the Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Gerald W.","family":"Dorn","sequence":"additional","affiliation":[{"name":"From the Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.10.013"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2282"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019481"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.813576"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01370-09"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.202176"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.217513"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.111.260752"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.727073"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.233528"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.220772"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti551"},{"key":"e_1_3_5_14_2","unstructured":"GeneGo. 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