Online Table. Some Circulating microRNAs Found Associated with Cardiovascular Diseases miRNA Misexpression Acute myocardial infarction (STEMI+NSTEMI) miR-1 Up-regulated in AMI patients within 4h of the onset of symptoms, peak at 8h Specimen Study Population Setting Ref. plasma 17 AMI patients and 25 controls Hospital admission (1) miR-1 Up-regulated in AMI patients, normalized at discharge plasma 93 AMI patients and 66 controls Hospital admission (2) miR-133 Up-regulated in AMI patients within 4h of the onset of symptoms, correlated with miR-328 and cTnI plasma 51 AMI patients and 28 controls Hospital Admission (3) miR-133a, miR-1 miR-133a and miR-1 are elevated early after the onset of symptoms; miR-133a is elevated also in UA and TT patients serum 29 ACS patients (18 STEMI, 3 NSTEMI, 8 UA patients) and 42 controls CCU (4) miR-208, miR499 Extensively elevated in AMI patients and markedly elevated in viral myocarditis plasma 32 AMI patients and 36 controls with atypical chest pain and positive stress test with normal coronary angiograms CCU (5) miR-208 Up-regulated in AMI patients within 4h of the onset of symptoms plasma 33 consecutive AMI-patients and 33 nonAMI controls Hospital admission (6) miR-499 Up-regulated in AMI patients within 3h of the onset of symptoms plasma 510 AMI patients (113 NSTEMI, 397 STEMI) and 87 controls CCU (7) mIR-663b, miR1291, miR-145, miR-30c Up-regulated in AMI patients and correlated with cTnI levels whole blood 20 AMI patients and 20 controls CCU (8) miR-30a, miR195 Up-regulated in AMI patients plasma 18 AMI patients and 30 controls Hospital admission or CCU (9) miR-1 and miR133a Significantly increased at early after AMI serum 21 TASH patients Cath Lab (10) miR-1 Regulates the level of fatty acid-binding protein-3 (FABP3), a small cytoplasmic protein involved in cardiac metabolism and released into the bloodstream by CMs following ischemic episodes plasma and biopsies patients with acromegaly or Growth Hormone Deficiency and 5 patients with aortic valve stenosis Hospital admission (11) plasma 33 STEMI patients and 17 controls CCU (12) Correlated with relevant CMR markers unable to prevent events serum 216 consecutive STEMI patients Cath Lab (13) Up-regulated in AMI plasma 37 TTC patients, 27 STEMI patients and 28 controls Hospital admission (14) 92 NSTEMI patients + 81 AHF patients without AMI and 99 controls CCU (15) plasma 19 NSTEMI patients+ 31 CAD patients + 7 controls Cath Lab (16) plasma and serum 36 CAD patients + 17 controls CCU (17) plasma 250 populationbased individuals (Bruneck Study) Hospital admission (18) plasma 822 populationbased individuals Hospital admission (19) ST-Elevated myocardial infarction miR-1, miR-133a, Up-regulated in STEMI patients miR-133b, miR499-5p miR-133a miR-1, miR133a/b, miR208a/b, and miR499–5p Acute coronary syndrome and non S-T myocardial infarction miR-499-5p Up-regulated in NSTEMI patients vs. plasma AHF patients and controls miR-133a, miR499 Released from the heart into the coronary circulation on myocardial injury in patients with CAD Coronary artery disease miR-126, miR-17, Down-regulated in CAD patients miR-92a, and miR-155 miR-126 Positive association with subsequent AMI Vascular disease: diabetes mellitus, aortic aneurysm miR-126 Down-regulated in DM miR-1, miR-21 miRNA abundance may be different in BAV and TAV Pulmonary hypertension miR-21, miRmiR-1, miR-26a, miR-29c down130a, miR-133b, regulated in PAH; miR-191, miRmiR-21, miR-130a, miR-133b, miR-191, 204, miR-208b, miR-204, miR-208b up-regulated in PAH miR-1, miR-26a, miR-29c miR-150 Reduced levels in PAH, and correlated with survival Acute pulmonary embolism miR-134 Elevated in APE patients plasma and aortic tissue 42 AA (21 BAV and 21 TAV) patients + 10 controls OR (20) whole blood 32 PAH patients + 16 controls Hospital admission (21) plasma 175 PAH patients + 18 controls Hospital admission (22) plasma 32 APE Hospital (23) patients + 32 admission controls +22 dyspnoic nonAPE patients AA, aortic aneurysm; AMI, acute myocardial infarction; APE, acute pulmonary embolism; BAV, bicuspid aortic valve; CAD, coronary artery disease; CCU, coronary care unit; DCM, dilated cardiomyopathy; DM, diabetes mellitus; ED, emergency department; HCM, hypertrophic cardiomyopathy; NSTEMI, non-ST elevated myocardial infarction; NYHA, New York Hear Association; PAH, pulmonary artery hypertension; PBMCs, peripheral blood mononuclear cells; STEMI, ST-elevated myocardial infarction; TASH, transcoronary ablation of septal hypertrophy; TAV, tricuspid aortic valve; TTC, Tako-Tsubo cardiomyopathy; UA, unstable angina. Supplementary References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. Long G, Wang F, Duan Q, et al. Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction. Int J Biol Sci 2012;8:811-8. Ai J, Zhang R, Li Y, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 2010;391:73-7. Wang R, Li N, Zhang Y, Ran Y, Pu J. Circulating microRNAs are promising novel biomarkers of acute myocardial infarction. Intern Med 2011;50:1789-95. Kuwabara Y, Ono K, Horie T, et al. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet 2011;4:44654. Corsten MF, Dennert R, Jochems S, et al. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 2010;3:499-506. Wang GK, Zhu JQ, Zhang JT, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010;31:659-66. Devaux Y, Vausort M, Goretti E, et al. Use of circulating microRNAs to diagnose acute myocardial infarction. Clin Chem 2012;58:559-67. Meder B, Keller A, Vogel B, et al. MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol 2011;106:13-23. Long G, Wang F, Duan Q, et al. Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PlOS One 2012;7:e50926. Liebetrau C, Mollmann H, Dorr O, et al. Release Kinetics of Circulating Muscle-Enriched MicroRNAs in Patients Undergoing Transcoronary Ablation of Septal Hypertrophy. J Am Coll Cardiol 2013;62:992-8. Varrone F, Gargano B, Carullo P, et al. The circulating level of FABP3 is an indirect biomarker of microRNA-1. J Am Coll Cardiol 2013;61:88-95. D'Alessandra Y, Devanna P, Limana F, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 2010;31:2765-73. Eitel I, Adams V, Dieterich P, et al. Relation of circulating MicroRNA-133a concentrations with myocardial damage and clinical prognosis in ST-elevation myocardial infarction. Am Heart J 2012;164:706-14. Jaguszewski M, Osipova J, Ghadri JR, et al. A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J 2013. Olivieri F, Antonicelli R, Lorenzi M, et al. Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. Int J Cardiol 2013;167:531-6. De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM. Transcoronary concentration gradients of circulating microRNAs. Circulation 2011;124:1936-44. Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res 2010;107:677-84. Zampetaki A, Willeit P, Tilling L, et al. Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 2012;60:290-9. Zampetaki A, Kiechl S, Drozdov I, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 2010;107:810-7. Ikonomidis JS, Ivey CR, Wheeler JB, et al. Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease. J Thorac Cardiovasc Surg 2013;145:1326-33. Wei C, Henderson H, Spradley C, et al. Circulating miRNAs as potential marker for pulmonary hypertension. PlOS One 2013;8:e64396. Rhodes CJ, Wharton J, Boon RA, et al. Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension. Am J Respir Crit Care Med 2013;187:294-302. 23. Xiao J, Jing Z-C, Ellinor P, et al. MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute pulmonary embolism. Journal of Translational Medicine 2011;9:159.