{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:40:02Z","timestamp":1789429202526,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation","award":["465409392"],"award-info":[{"award-number":["465409392"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiac injury after severe trauma is associated with higher mortality in polytrauma patients. Recent evidence suggests that miRNAs play a key role in cardiac pathophysiology and could serve as potential markers of cardiac damage after polytrauma. To explore this hypothesis, plasma miRNA profiles from polytrauma patients (ISS \u2265 16) with and without cardiac injury, stratified by troponin T levels (TnT, &gt; 50 pg\/mL vs. &lt; 12 pg\/mL), were analysed using NGS and validated via RT-qPCR. Five miRNAs (miR-122-5p, miR-424-5p, miR-885-5p, miR-194-5p, and miR-499a-5p) were found to be significantly upregulated in polytrauma patients with elevated TnT levels. miR-122-5p was associated with markers of right ventricular dysfunction (TAPSE) and left ventricular hypertrophy (IVS\/LVPW), while miR-885-5p correlated with left ventricular hypertrophy (IVS\/LVPW) and diastolic dysfunction (E\/E\u2019 ratio). In vitro, miR-194-5p mimic and miR-499a-5p mimic exhibited more active roles in cardiomyocyte injury by increasing caspase-3\/7 activity and\/or enhancing caspase-1 activity. Notably, the miR-194-5p mimic significantly enhanced the cytotoxic effects of the polytrauma cocktail, while miR-499a-5p boosted effects of LPS\/nigericin stimulation in cardiomyocytes. Our findings identify miR-122-5p and miR-885-5p as potential biomarkers reflecting the cardiomyocyte response to polytrauma-induced inflammation, while miR-499a-5p and miR-194-5p appear to play a direct role in myocardial injury after polytrauma.<\/jats:p>","DOI":"10.3390\/cells14040300","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T03:47:06Z","timestamp":1739850426000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual Roles of Plasma miRNAs in Myocardial Injuries After Polytrauma: miR-122-5p and miR-885-5p Reflect Inflammatory Response, While miR-499a-5p and miR-194-5p Contribute to Cardiomyocyte Damage"],"prefix":"10.3390","volume":"14","author":[{"given":"Jiaoyan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmila","family":"Leppik","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Sztulman","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-4965","authenticated-orcid":false,"given":"Roberta","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-7854","authenticated-orcid":false,"given":"Victoria","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewin-Caspar","family":"Busse","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kontaxi","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-4032","authenticated-orcid":false,"given":"Dirk","family":"Henrich","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-2910","authenticated-orcid":false,"given":"Ingo","family":"Marzi","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13049-022-01058-6","article-title":"Thoracic injuries in trauma patients: Epidemiology and its influence on mortality","volume":"30","author":"Lundin","year":"2022","journal-title":"Scand. J. Trauma. Resusc. Emerg. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00068-005-2033-9","article-title":"Chest Injuries in Polytrauma","volume":"31","author":"Arbes","year":"2005","journal-title":"Eur. J. Trauma."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hanschen, M., Kanz, K.G., Kirchhoff, C., Khalil, P.N., Wierer, M., van Griensven, M., Laugwitz, K.L., Biberthaler, P., Lefering, R., and Huber-Wagner, S. (2015). Blunt Cardiac Injury in the Severely Injured\u2014A Retrospective Multicentre Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131362"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Weber, B., Lackner, I., Gebhard, F., Miclau, T., and Kalbitz, M. (2021). Trauma, a Matter of the Heart-Molecular Mechanism of Post-Traumatic Cardiac Dysfunction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020737"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.clinbiochem.2017.02.007","article-title":"Clearance of cardiac troponin T with and without kidney function","volume":"50","author":"Starnberg","year":"2017","journal-title":"Clin. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1161\/CIRCRESAHA.110.218297","article-title":"MiR423-5p as a circulating biomarker for heart failure","volume":"106","author":"Tijsen","year":"2010","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20355","DOI":"10.3390\/ijms151120355","article-title":"Circulating microRNA-19a as a potential novel biomarker for diagnosis of acute myocardial infarction","volume":"15","author":"Zhong","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1373\/clinchem.2010.144121","article-title":"Plasma microRNA 499 as a biomarker of acute myocardial infarction","volume":"56","author":"Adachi","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/eurheartj\/ehq013","article-title":"Circulating microRNA: A novel potential biomarker for early diagnosis of acute myocardial infarction in humans","volume":"31","author":"Wang","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/CIRCULATIONAHA.123.067373","article-title":"RNA Therapeutics for the Cardiovascular System","volume":"149","author":"Dzau","year":"2024","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"239ps233","DOI":"10.1126\/scitranslmed.3009008","article-title":"MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease","volume":"6","author":"Olson","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature09783","article-title":"Pervasive roles of microRNAs in cardiovascular biology","volume":"469","author":"Small","year":"2011","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1161\/CIRCRESAHA.108.192872","article-title":"MicroRNA regulation of cardiovascular development","volume":"104","author":"Cordes","year":"2009","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kansakar, U., Varzideh, F., Mone, P., Jankauskas, S.S., and Santulli, G. (2022). Functional Role of microRNAs in Regulating Cardiomyocyte Death. Cells, 11.","DOI":"10.3390\/cells11060983"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1007\/s00204-016-1828-2","article-title":"Recent progress toward the use of circulating microRNAs as clinical biomarkers","volume":"90","author":"Ghai","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10513","DOI":"10.1073\/pnas.0804549105","article-title":"Circulating microRNAs as stable blood-based markers for cancer detection","volume":"105","author":"Mitchell","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rogobete, A.F., Sandesc, D., Bedreag, O.H., Papurica, M., Popovici, S.E., Bratu, T., Popoiu, C.M., Nitu, R., Dragomir, T., and HIM, A.A. (2018). MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients. Cells, 7.","DOI":"10.3390\/cells7120271"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_22","unstructured":"D\u00f6rr, M., Goder, S., Bahls, M., and Lehnert, K. (2023). DZHK-SOP-C-08: Transthoracic Echocardiography, DZHK."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1097\/SHK.0000000000001400","article-title":"Cardiac Glucose and Fatty Acid Transport After Experimental Mono- and Polytrauma","volume":"53","author":"Lackner","year":"2020","journal-title":"Shock"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D1327","DOI":"10.1093\/nar\/gkad717","article-title":"HMDD v4.0: A database for experimentally supported human microRNA-disease associations","volume":"52","author":"Cui","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/1354750X.2018.1499804","article-title":"The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest","volume":"24","author":"Gilje","year":"2019","journal-title":"Biomarkers"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1080\/21655979.2021.1926201","article-title":"Inhibition of micro RNA miR-122-5p prevents lipopolysaccharide-induced myocardial injury by inhibiting oxidative stress, inflammation and apoptosis via targeting GIT1","volume":"12","author":"Song","year":"2021","journal-title":"Bioengineered"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: Mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108053","DOI":"10.1016\/j.pharmthera.2021.108053","article-title":"Targeting the NLRP3 inflammasome in cardiovascular diseases","volume":"236","author":"Toldo","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Dai, S., Ye, B., Zhong, L., Chen, Y., Hong, G., Zhao, G., Su, L., and Lu, Z. (2021). GSDMD Mediates LPS-Induced Septic Myocardial Dysfunction by Regulating ROS-dependent NLRP3 Inflammasome Activation. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.779432"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/SHK.0b013e31823f1811","article-title":"Plasma levels of liver-specific miR-122 is massively increased in a porcine cardiogenic shock model and attenuated by hypothermia","volume":"37","author":"Andersson","year":"2012","journal-title":"Shock"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"ehac544.823","DOI":"10.1093\/eurheartj\/ehac544.823","article-title":"Circulating microRNA-122-5p is associated with a lack of improvement in left-ventricular function after TAVR and regulates viability of cardiomyocytes via extracellular vesicles","volume":"43","author":"Hosen","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tu, G.W., Ma, J.F., Li, J.K., Su, Y., Luo, J.C., Hao, G.W., Luo, M.H., Cao, Y.R., Zhang, Y., and Luo, Z. (2022). Exosome-Derived From Sepsis Patients\u2019 Blood Promoted Pyroptosis of Cardiomyocytes by Regulating miR-885-5p\/HMBOX1. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.774193"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, J., Wei, T., Zhang, W., Chu, Y., Zhang, D., Zhang, M., Hu, J., Ji, Z., and Hao, Q. (2024). Inhibition of miR-194-5p avoids DUSP9 downregulation thus limiting sepsis-induced cardiomyopathy. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-71166-z"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Baulina, N., Pisklova, M., Kiselev, I., Chumakova, O., Zateyshchikov, D., and Favorova, O. (2022). Circulating miR-499a-5p Is a Potential Biomarker of MYH7-Associated Hypertrophic Cardiomyopathy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073791"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Fa, H., Xiao, D., Chang, W., Ding, L., Yang, L., Wang, Y., Wang, M., and Wang, J. (2022). MicroRNA-194-5p Attenuates Doxorubicin-Induced Cardiomyocyte Apoptosis and Endoplasmic Reticulum Stress by Targeting P21-Activated Kinase 2. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.815916"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"654","DOI":"10.21037\/atm-21-807","article-title":"miR-194-5p protects against myocardial ischemia\/reperfusion injury via MAPK1\/PTEN\/AKT pathway","volume":"9","author":"Zhang","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11380","DOI":"10.1002\/jcp.27795","article-title":"Identification of microRNAs related to myocardial ischemic reperfusion injury","volume":"234","author":"Liu","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4161\/rna.28300","article-title":"miR-499 protects cardiomyocytes from H2O2-induced apoptosis via its effects on Pdcd4 and Pacs2","volume":"11","author":"Wang","year":"2014","journal-title":"RNA Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/ejhf.517","article-title":"The transcardiac gradient of cardio-microRNAs in the failing heart","volume":"18","author":"Marques","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.yjmcc.2016.05.009","article-title":"Circulating microRNAs predict future fatal myocardial infarction in healthy individuals\u2014The HUNT study","volume":"97","author":"Bye","year":"2016","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11171","DOI":"10.3390\/ijms140611171","article-title":"Fluctuation of global gene expression by endogenous miRNA response to the introduction of an exogenous miRNA","volume":"14","author":"Nagata","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, L., He, X., Liu, M., Yun, L., and Cong, B. (2022). Diagnostic value of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p in coronary artery disease-induced sudden cardiac death. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.944317"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCRESAHA.109.215566","article-title":"Circulating microRNAs in patients with coronary artery disease","volume":"107","author":"Fichtlscherer","year":"2010","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nm.2282","article-title":"miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1","volume":"17","author":"Wang","year":"2011","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.3748\/wjg.15.1665","article-title":"MicroRNA signatures in liver diseases","volume":"15","author":"Chen","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Groven, R.V.M., Greven, J., Mert, \u00dc., Horst, K., Zhao, Q., Blokhuis, T.J., Huber-Lang, M., Hildebrand, F., and van Griensven, M. (2023). Circulating miRNA expression in extracellular vesicles is associated with specific injuries after multiple trauma and surgical invasiveness. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1273612"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6162","DOI":"10.1073\/pnas.1814139116","article-title":"Injured liver-released miRNA-122 elicits acute pulmonary inflammation via activating alveolar macrophage TLR7 signaling pathway","volume":"116","author":"Wang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1134\/S1819712424020132","article-title":"miR-885-5p Predicts the Risk and Development of Intracranial Hemorrhage in Traumatic Brain Injury and Regulates Inflammation in Microglia","volume":"18","author":"Litao","year":"2024","journal-title":"Neurochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semcdb.2017.12.011","article-title":"Secretory microRNAs as biomarkers of cancer","volume":"78","author":"Kai","year":"2018","journal-title":"Semin. Cell Dev. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/4\/300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:36:36Z","timestamp":1760027796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/4\/300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,18]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cells14040300"],"URL":"https:\/\/doi.org\/10.3390\/cells14040300","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,18]]}}}