{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:48:51Z","timestamp":1786121331549,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"\n Background<\/jats:title>\n \n Cardiac contractility is regulated by two myosin heavy chain (MHC) protein isoforms,\n \u03b1<\/jats:italic>\n and \u03b2, encoded by the\n MYH6<\/jats:italic>\n and\n MYH7<\/jats:italic>\n genes. The intronic regions of these genes encode the microRNAs\n miR-208a<\/jats:italic>\n and\n miR-208b<\/jats:italic>\n , which are key regulators of cardiac hypertrophy. Functionally relevant long non-coding RNAs (lncRNAs) have also been identified at these loci, such as those transcribed in the antisense direction from the\n MYH7<\/jats:italic>\n gene, including the primary\n miR-208b<\/jats:italic>\n transcript (\n MHRT<\/jats:italic>\n ) originating from an internal\n MYH7<\/jats:italic>\n promoter. Additionally,\n MYH7B<\/jats:italic>\n , another cardiac sarcomeric myosin gene, serves as a precursor for\n miR-499a-5p<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n This study aimed to comprehensively analyse the expression profiles of\n MYH6, MYH7,<\/jats:italic>\n and\n MYH7B<\/jats:italic>\n genes, microRNAs (\n miR-208a-3p, miR-208b-3p, and miR-499a-5p<\/jats:italic>\n ), and the\n lncRNA MHRT<\/jats:italic>\n in non-failing and end-stage failing human left ventricles.\n <\/jats:p>\n <\/jats:sec>\n \n Subjects and methods<\/jats:title>\n \n The relative expression of these transcripts was measured using RT-qPCR in left ventricular samples from 5 non-failing controls and 24 patients with end-stage heart failure, including hypertrophic cardiomyopathy (HCM,\n n<\/jats:italic>\n \u2009=\u20094), dilated cardiomyopathy (DCM,\n n<\/jats:italic>\n \u2009=\u200910), and coronary artery disease (CAD,\n n<\/jats:italic>\n \u2009=\u200910). The findings were validated by comparison with two independent RNA-seq datasets (GSE141910 and GSE116250) for\n MYH6<\/jats:italic>\n ,\n MYH7<\/jats:italic>\n ,\n MYH7B<\/jats:italic>\n , and\n MHRT<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Statistical analysis of independent RNA-seq datasets confirmed strong correlations among\n MYH7, MYH7B,<\/jats:italic>\n and\n MHRT<\/jats:italic>\n transcripts (\n p<\/jats:italic>\n \u2009\u2264\u20090.0001), a trend also observed in our RT-qPCR cohort. A profound imbalance in the\n MYH7B\/miR-499-5p<\/jats:italic>\n ratio was identified, shifting from \u223c250:1 in non-failing controls to \u223c12\u201318:1 in failing hearts. The\n miR-208a-3p\/miR-208b-3p<\/jats:italic>\n expression ratio was heavily skewed toward\n miR-208b-3p<\/jats:italic>\n (\u223c50:1) in all groups, regardless of disease status.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our results suggest that\n MYH7, MYH7B<\/jats:italic>\n , and\n MHRT<\/jats:italic>\n transcripts exhibit coordinated expression patterns in human left ventricles, independent of pathological status. We further observed a dissociation between\n miR-208a-3p<\/jats:italic>\n and its host gene (\n MYH6<\/jats:italic>\n ) under physiological conditions and confirmed altered\n miR-499a-5p\/MYH7B<\/jats:italic>\n relationships, consistent with findings in murine models. Moreover, the expression of two regulatory genes,\n SOX6<\/jats:italic>\n and\n TARBP2<\/jats:italic>\n , known to modulate\n MYH7<\/jats:italic>\n and\n MYH7B<\/jats:italic>\n in mice, showed that\n SOX6<\/jats:italic>\n is upregulated in the left ventricles of all pathological groups.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1879458","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:22:15Z","timestamp":1786076535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated analysis of MYH6, MYH7, and MYH7B expression and their associated microRNAs in human end-stage heart failure"],"prefix":"10.3389","volume":"13","author":[{"given":"Zdenko","family":"\u010cerven\u00e1k","sequence":"first","affiliation":[{"name":"5th Department of Internal Medicine, Faculty of Medicine, Comenius University","place":["Bratislava, 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Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoleta","family":"Katreni\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Hulman","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Faculty of Medicine, Comenius University and National Institute of Cardiovascular Diseases (N\u00daSCH)","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ga\u017eov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University","place":["Bratislava, 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