{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:10:12Z","timestamp":1773382212371,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5\u201310 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p &lt; 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1\u20133.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2\u20133.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.<\/jats:p>","DOI":"10.3390\/ijms21217925","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T02:34:54Z","timestamp":1603679694000},"page":"7925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-0229","authenticated-orcid":false,"given":"Mikko","family":"H\u00e4nninen","sequence":"first","affiliation":[{"name":"Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toni","family":"J\u00e4ntti","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Helsinki and Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heli","family":"Tolppanen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Helsinki and Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heli","family":"Segersv\u00e4rd","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-243X","authenticated-orcid":false,"given":"Tuukka","family":"Tarvasm\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Helsinki and Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Lassus","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Helsinki and Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-7729","authenticated-orcid":false,"given":"M\u00e9lanie","family":"Vausort","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5321-8543","authenticated-orcid":false,"given":"Yvan","family":"Devaux","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Sionis","sequence":"additional","affiliation":[{"name":"Intensive Cardiac Care Unit, Cardiology Department, Biomedical Research Institute IIB-SantPau, Hospital de la Santa Creu i Sant Pau, Universidad Aut\u00f3noma de Barcelona, 08041 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilkka","family":"Tikkanen","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, 00029 Helsinki, Finland"},{"name":"Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veli-Pekka","family":"Harjola","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, University of Helsinki and Department of Emergency Services and Medicine, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-6573","authenticated-orcid":false,"given":"P\u00e4ivi","family":"Lakkisto","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, 00029 Helsinki, Finland"},{"name":"Department of Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the CardShock Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1161\/CIRCULATIONAHA.106.613596","article-title":"Cardiogenic shock: Current concepts and improving outcomes","volume":"117","author":"Reynolds","year":"2008","journal-title":"Circulation"},{"key":"ref_2","first-page":"e232","article-title":"Contemporary management of cardiogenic shock: A scientific statement from the American Heart Association","volume":"136","author":"Katz","year":"2017","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1056\/NEJMoa1208410","article-title":"Intraaortic balloon support for myocardial infarction with cardiogenic shock","volume":"367","author":"Thiele","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/eurheartj\/ehv051","article-title":"Management of cardiogenic shock","volume":"36","author":"Thiele","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/S0735-1097(00)00879-2","article-title":"Cardiogenic shock complicating acute myocardial infarction\u2014Etiologies, management and outcome: A report from the SHOCK Trial Registry","volume":"36","author":"Hochman","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/ejhf.260","article-title":"Clinical picture and risk prediction of short-term mortality in cardiogenic shock","volume":"17","author":"Harjola","year":"2015","journal-title":"Eur. J. Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2015.05.001","article-title":"An overview of microRNAs","volume":"87","author":"Hammond","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1161\/CIRCRESAHA.111.247452","article-title":"Circulating MicroRNAs: Novel biomarkers and extracellular communicators in cardiovascular disease?","volume":"110","author":"Creemers","year":"2012","journal-title":"Circ. Res."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13148-018-0492-1","article-title":"Circulating microRNAs as potential cancer biomarkers: The advantage and disadvantage","volume":"10","author":"Wang","year":"2018","journal-title":"Clin. Epigenetics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s12265-010-9169-7","article-title":"MicroRNA-21 in cardiovascular disease","volume":"3","author":"Cheng","year":"2010","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"706","DOI":"10.4161\/rna.8.5.16154","article-title":"Regulation and function of miRNA-21 in health and disease","volume":"8","author":"Kumarswamy","year":"2011","journal-title":"RNA Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29514","DOI":"10.1074\/jbc.M109.027896","article-title":"MicroRNA expression signature and the role of MicroRNA-21 in the early phase of acute myocardial infarction","volume":"284","author":"Dong","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, C.-H., Hsu, S.-Y., Chiu, C.-C., and Leu, S. (2019). MicroRNA-21 mediates the protective effect of cardiomyocyte-derived conditioned medium on ameliorating myocardial infarction in rats. Cells, 8.","DOI":"10.3390\/cells8080935"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.12659\/MSM.904933","article-title":"miRNA-21 expression in the serum of elderly patients with acute myocardial infarction","volume":"23","author":"Wang","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0960-9822(02)00809-6","article-title":"Identification of tissue-specific microRNAs from mouse","volume":"12","author":"Rauhut","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1172\/JCI63455","article-title":"MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis","volume":"122","author":"Tsai","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1373\/clinchem.2010.147850","article-title":"Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases","volume":"56","author":"Zhang","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1161\/CIRCGENETICS.110.957415","article-title":"Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease","volume":"3","author":"Corsten","year":"2010","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1161\/CIRCULATIONAHA.108.814145","article-title":"MicroRNA-320 is involved in the regulation of cardiac ischemia\/reperfusion injury by targeting heat-shock protein 20","volume":"119","author":"Ren","year":"2009","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s11658-018-0105-1","article-title":"MiR-320 regulates cardiomyocyte apoptosis induced by ischemia\u2013reperfusion injury by targeting AKIP1","volume":"23","author":"Tian","year":"2018","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/joim.12183","article-title":"Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain","volume":"277","author":"Devaux","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1253\/circj.CJ-16-0568","article-title":"Circulating miR-122-5p\/miR-133B ratio is a specific early prognostic biomarker in acute myocardial infarction","volume":"80","author":"Costa","year":"2016","journal-title":"Circ. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4149\/BLL_2018_064","article-title":"MicroRNAs in pathophysiology of acute myocardial infarction and cardiogenic shock","volume":"119","author":"Goldbergova","year":"2018","journal-title":"Bratisl. Med. J."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/ehf2.12377","article-title":"Circulating levels of microRNA 423-5p are associated with 90 day mortality in cardiogenic shock","volume":"6","author":"Tolppanen","year":"2019","journal-title":"ESC Heart Fail."},{"key":"ref_29","first-page":"783","article-title":"Circulating MiRNA Dynamics in ST-Segment Elevation Myocardial Infarction-driven Cardiogenic Shock","volume":"72","author":"Rueda","year":"2019","journal-title":"Rev. Espa\u00f1ola Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kura, B., Kalocayova, B., Devaux, Y., and Bartekova, M. (2020). Potential clinical implications of mir-1 and mir-21 in heart disease and cardioprotection. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030700"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1016\/j.febslet.2014.05.067","article-title":"A feedback regulatory loop between HIF-1\u03b1 and miR-21 in response to hypoxia in cardiomyocytes","volume":"588","author":"Liu","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/cvr\/cvq082","article-title":"Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia\/reperfusion injury via anti-apoptosis through its target PDCD4","volume":"87","author":"Cheng","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/carcin\/bgt378","article-title":"miR-320a suppresses colorectal cancer progression by targeting Rac1","volume":"35","author":"Zhao","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29275","DOI":"10.18632\/oncotarget.8676","article-title":"MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27KIP1 axis","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.canlet.2017.03.004","article-title":"Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis","volume":"397","author":"Zhang","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Galeano-Otero, I., Del Toro, R., Guisado, A., D\u00edaz, I., Mayoral-Gonz\u00e1lez, I., Guerrero-M\u00e1rquez, F., Guti\u00e9rrez-Carretero, E., Casquero-Dom\u00ednguez, S., D\u00edaz-de la Llera, L., and Bar\u00f3n-Esquivias, G. (2020). Circulating miR-320a as a predictive biomarker for left ventricular remodelling in STEMI patients undergoing primary percutaneous coronary intervention. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041051"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1177\/2048872617702505","article-title":"Altered mental status predicts mortality in cardiogenic shock\u2014Results from the CardShock study","volume":"7","author":"Kataja","year":"2018","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1160\/TH12-02-0097","article-title":"Analytical challenges and technical limitations in assessing circulating MiRNAs","volume":"108","author":"Zampetaki","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000328869","article-title":"Cardiospecific microRNA plasma levels correlate with troponin and cardiac function in patients with ST elevation myocardial infarction, are selectively dependent on renal elimination, and can be detected in urine samples","volume":"118","author":"Andersson","year":"2011","journal-title":"Cardiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1093\/ndt\/gfr485","article-title":"Circulating microRNA expression is reduced in chronic kidney disease","volume":"26","author":"Neal","year":"2011","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cca.2019.09.005","article-title":"Plasma MicroRNA as a novel diagnostic","volume":"499","author":"Szelenberger","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/j.jacc.2020.02.041","article-title":"AntimiR-21 prevents myocardial dysfunction in a pig model of ischemia\/reperfusion injury","volume":"75","author":"Hinkel","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/ejhf.958","article-title":"Acute kidney injury in cardiogenic shock: Definitions, incidence, haemodynamic alterations, and mortality","volume":"20","author":"Haapio","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1373\/clinchem.2011.173823","article-title":"Use of circulating microRNAs to diagnose acute myocardial infarction","volume":"58","author":"Devaux","year":"2012","journal-title":"Clin. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/7925\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:00Z","timestamp":1760178480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/7925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,26]]},"references-count":45,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21217925"],"URL":"https:\/\/doi.org\/10.3390\/ijms21217925","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,26]]}}}