Circulating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease
2010; Lippincott Williams & Wilkins; Volume: 3; Issue: 5 Linguagem: Inglês
10.1161/circgenetics.110.958363
ISSN1942-325X
AutoresShashi Kumar Gupta, Claudia Bang, Thomas Thum,
Tópico(s)Circular RNAs in diseases
ResumoHomeCirculation: Cardiovascular GeneticsVol. 3, No. 5Circulating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease Free AccessResearch ArticlePDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease Shashi K. Gupta, Claudia Bang and Thomas Thum Shashi K. GuptaShashi K. Gupta From the Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany. , Claudia BangClaudia Bang From the Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany. and Thomas ThumThomas Thum From the Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany. Originally published1 Oct 2010https://doi.org/10.1161/CIRCGENETICS.110.958363Circulation: Cardiovascular Genetics. 2010;3:484–488IntroductionMicroRNAs (miRNAs) comprise a class of small, noncoding RNAs that control expression of complementary target mRNAs. Dysregulation of intracellular miRNA expression has been described in various diseases, including a number of cardiovascular conditions. Functional studies have shown a role for miRNAs in cardiac fibrosis, hypertrophy, angiogenesis, and heart failure.1–3 These findings suggest a new therapeutic entry point for cardiac disease and illustrate the broad therapeutic potential of miRNA modulation. Initial reports have detected circulating extracellular miRNAs in the serum/plasma of patients with cancer.4 Despite the existence of RNases, miRNAs remain stable in serum and other body fluids. One explanation is the inclusion of miRNAs into lipid or lipoprotein complexes such as exosomes5 or microvesicles.6 Subsequently, altered concentrations of miRNAs have been found in patients with various cardiovascular diseases. Here, we review the current knowledge about circulating miRNAs during coronary artery disease (CAD), myocardial infarction, and heart failure (Table). A further new and exciting function of circulating miRNAs in the cardiovascular system may be their potential to serve as paracrine signaling molecules.7Secretion, Stability, and Potential Function of Circulating MiRNAsThe detection of circulating miRNAs in serum/plasma8,9 suggests that miRNAs may fulfill biological functions outside the cell and serve as potential biomarkers for diseases. Circulating miRNAs are protected from RNase-dependent degradation by several mechanisms, including their inclusion in microvesicles, exosomes, and apoptotic bodies as well as through the formation of protein-miRNA complexes resistant to degradation (Figure). In addition, circulating miRNAs are quite stable even after multiple freeze-thaw cycles.8 Recent studies have shown that miRNAs are actively secreted in microvesicles or exosomes from different cell types.6,10 Despite the current knowledge about the existence of circulating miRNAs and the intercellular transfer of miRNAs from donor cells to recipient cells, the underlying mechanisms of the cellular secretion of miRNAs are not fully understood. MiRNA loading into exosomes depends on the association of the RNA-induced silencing complex with multivesicular bodies.11,12 Neutral sphingomyelinase 2, which regulates the biosynthesis of ceramide, was identified to control, at least in part, the secretion of miRNAs.13 Cells that have been confirmed as secreting miRNAs through exosomes include mast cells5 and embryonic stem cells. For the latter, it has been shown that miRNA-enriched microvesicles can be transferred to mouse embryonic fibroblasts in vitro, thus influencing the expression of genes in adjacent cells.14 Further, miRNAs from Epstein-Barr virus-infected cells are transported to uninfected recipient cells through exosomes.7 Brain microvascular endothelial cells are able to take up glioblastoma-derived microvesicles enriched with mRNAs and miRNAs with subsequent alteration of the genetic endothelial program.10 Exosomes have been identified as an active component of conditioned medium from human embryonic stem cell-derived mesenchymal stem cells. Injection of such exosomes into a pig or murine model of cardiac ischemia/reperfusion injury has resulted in reduced cardiac damage and improved outcome.15,16 Cardiomyocyte progenitor cells release exosomes that stimulate the migration of endothelial cells.17 MiRNAs also can be released directly from damaged cells (eg, after myocardial infarction).18 Endothelial-derived apoptotic bodies enriched with miR-126 can be transported into atherosclerotic lesions and convey paracrine alarm signals to recipient vascular cells that trigger the recruitment of progenitor cells and alleviate atherosclerosis.17 As noted, miRNAs can be protected from degradation by the formation of specific protein-miRNA complexes. Mammalian cells release a significant number of RNA-binding proteins into the culture medium after serum deprivation.19 For instance, nucleophosmin 1 is able to bind miRNAs and might be involved in miRNA exportation, packaging, and protection of extracellular miRNAs from degradation.Download figureDownload PowerPointFigure. Mobilization and uptake of miRNAs in cardiovascular disease. Top and middle: Cardiac stress, such as cardiac ischemia and pressure/volume overload, leads to mobilization of miRNAs by either active secretory mechanisms through exosomes, microvesicles, and apoptotic bodies or passive secretion on cell necrosis. Bottom: Possible mechanisms of intercellular communication by exosomes during cardiac disease. (1) Exosomes may bind to the surface of target cells through receptor-ligand interaction, resulting in intracellular stimulation of genetic pathways. (2) Exosomes can fuse putatively with the target cell membrane and release their genetic contents inside recipient cells. The exosomal content, including proteins, mRNAs, and miRNAs, leads to altered genetic activity. (3) Exosomes also may bind to surface receptors on target cells following internalization by the target cells through endocytosis. After internalization, exosomes can fuse with the membranes of endosomes, leading to a release of their content into the cytosol of target cells, or remain segregated within endosomes and transfer the content to lysosomes.How can intercellular communication be mediated by exosomes? Exosomes released from a specific cell type may act as signaling complexes through the binding of exosomal membrane proteins with a surface receptor on target cells, resulting in intracellular stimulation (Figure).20,21 Alternatively, exosomes may bind to surface receptors on target cells with subsequent endocytotic internalization by the recipient cells (Figure).22 After internalization, exosomes can fuse with the membranes of endosomes, leading to release of their contents into the cytosol of target cells. Exosomes can remain segregated within endosomes and may transfer their content to lysosomes or may be released within the cells following fusion with the plasma membrane.22 Finally, exosomes can fuse with the target cell membrane and release their genetic contents inside the recipient cells in a nonselective manner (Figure).22 Circulating extracellular miRNAs likely represent a novel mechanism of intercellular communication. Which of the proposed mechanisms is mainly involved in the release of miRNAs and paracrine intercellular communication during cardiac disease remains to be determined.Detection, Quantification, and Normalization of Circulating MiRNAsThe use of circulating miRNAs as potential biomarkers in clinical scenarios depends on the sensitivity of methods used to detect them. Real-time quantitative reverse transcriptase-polymerase chain reaction is the most common and sensitive method used to date to quantify circulating miRNAs. Detailed descriptions of the methods for quantification of miRNAs in plasma or serum are available.23 Quantification of circulating miRNAs with high sensitivity is challenging because of (1) the very low amounts of RNA recovered from plasma or serum and (2) the lack of proper endogenous controls for normalization. However, because the RNA yield from plasma/serum is very low, accurate normalization procedures are important. The use of spiked-in control miRNAs is helpful in normalizing for isolation differences. Synthetic Caenorhabditis elegans miRNAs (such as miR-39, miR-54, and miR-238) were added after denaturation of plasma/serum during RNA isolation. Several other endogenous circulating miRNAs also can be used for normalization, such as miR-17-5p,24 miR-1249,25 U6,18 5S rRNA,26 miR-454, and RNU6b,8 although it cannot be ruled out that there are changes of the concentration in different patient populations on medication or with cardiovascular risk factors.Circulating MiRNAs as Emerging Biomarkers of Cardiovascular DiseaseCirculating miRNAs may have great potential for use as clinical biomarkers because easy, noninvasive detection in various medical conditions is possible. Circulating miRNAs have been shown as biomarkers in various diseases, including cancer27 where they also are of prognostic relevance. There is now growing evidence that circulating miRNAs also can be used as biomarkers in cardiovascular diseases (Table).Table. Overview of Circulating miRNAs in Various Cardiovascular DiseasesDisease TypemiRNAs UpregulatedmiRNAs DownregulatedTime PointNo. SamplesSpeciesCorrelationRef No.AMImiR-1, miR-133a, miR-133b, miR-499-5pmiR-122, miR-375517±309 min33 STEMI, 17 healthyHumanCardiac TnI, except for miR-499-5p24AMImiR-208a, miR-1, miR-133a, miR-4994.8±3.5 h33 AMI and non-AMI, 30 healthyHuman32AMImiR-49948 h9 AMI, 5 UAP, 9 CHF, 10 healthyHuman31AMImiR-18.5±3.82 h31 AMI, 20 healthyHumanCK-MB30AMImiR-193 AMI, 66 healthyHumanQRS widening18AMImiR-208b, miR-499, miR-133amiR-22312 h36 AMI, 36 healthyHumanCardiac TnI, CPK except for miR-22333VMmiR-208b, miR-499 (acute VM)14 acute, 20 post-VM, 20 healthyHumanWith severity of VM33HF acutemiR-499, miR-12233, 34 healthyHuman33HF diastolic20 hypertension, 39 diastolic dysfunction, 20 healthyHumanmiR-133a correlated to NT-proBNP33HFmiR-423-5p30 HF, 20 non-HF, 39 healthyHumanNT-proBNP, EF25CADmiR-133a, miR-208amiR-126, miR-17, miR-92a, miR-155, miR-14567 CAD, 31 healthyHumanStatin therapy28Type 2 diabetesmiR-126822 DMHuman29LAD ligationmiR-1, miR-133a, miR-133b, miR-499-5p, miR-208a18 h, 6 h, 18 h, 24 h, 3 h4–5Mice24LAD ligationmiR-208a3 h6Rat32LAD ligationmiR-16 h12RatMyocardial infarct size30Isoproterenol- induced myocardial injurymiR-2083 h8RatCardiac TnI26AMI indicates acute myocardial infarction; CAD, coronary artery disease; CHF, congestive heart failure; CK, creatine kinase; DM, diabetes mellitus; EF, ejection fraction; HF, heart failure; LAD, left anterior descending coronary artery; NT-proBNP, N-terminal prohormone brain natriuretic peptide; STEMI, ST-segment elevated myocardial infarction; UAP, unstable angina pectoris; VM, viral myocarditis.CAD and Cardiovascular Risk FactorsFichtlscherer et al28 reported reduced levels of miR-126, members of the miR-17-92 cluster, inflammation-related miR-155, and smooth muscle-enriched miR-145 in patients with CAD compared with healthy controls. In contrast, cardiac muscle-enriched miRNAs (miR-133a, miR-208a) tended to be higher in patients with CAD. Correlation studies revealed that vascular and inflammation-linked miRNAs were altered by vasculoprotective therapies with inhibitors of the renin-angiotensin system, aspirin, and statins. There is additional evidence that cardiac risk factors affect circulating miRNA levels. It was shown that patients suffering from prevalent diabetes have significantly decreased levels of miR-20b, miR-21, miR-24, miR-15a, miR-126, miR-191, miR-197, miR-223, miR-320, and miR-486 but a modest increase of miR-28–3p.29 MiR-126 data were confirmed in 822 patients in univariate and multivariate analyses. In patients with diabetes, the reduction of miR-126 was confined to circulating vesicles in plasma.Myocardial InfarctionIn a cohort of 93 patients with acute myocardial infarction (AMI), the muscle-enriched miRNA miR-1 was significantly upregulated in the circulation compared to non-AMI controls.18 MiR-1 levels correlated with abnormal QRS widening in patients with AMI, whereas no correlation was found with ST-segment alterations or levels of cardiac troponin (Tn) I or creatine kinase (CK) MB. MiRNA-1 also may serve as a potential predictor of AMI. Other studies have shown miR-1 to be upregulated in AMI, but in contrast to Ai et al,18 these studies demonstrated a positive correlation of miR-1 levels with CK-M levels,30 whereas D'Alessandra et al24 showed that miR-1 upregulation in patients with AMI correlates with cardiac TnI levels. Additional miRNAs that were found to be upregulated in patients with AMI (ST-segment elevation myocardial infarction) include miR-133a, miR-133b, miR-208b, miR-499, and miR-499-5p,24,31–33 whereas miR-122, miR-223, and miR-375 were lower than in controls.24,33 Plasma levels of heart-specific miR-208a became detectable in patients with AMI with a detection sensitivity of 90.9% but were undetectable in healthy controls.32 A parallel analysis of miR-208a along with TnI measurements 4 hours after the onset of symptoms showed miR-208a to be detectable in all affected individuals, whereas TnI was seen only in 85% of patients.32 MiR-208b and miR-499 correlated with TnT levels in patients with AMI, suggesting that miR-208a, miR-208b, miR-499, and other miRNAs may be alternatives or even superior to conventional biomarkers for the early detection of AMI (see Limitations section).Heart Failure and Viral MyocarditisMiRNAs have been shown to play an important role in mediating the transcriptional changes observed during heart failure, so a change in profile of circulating miRNAs may be expected in this context.1 Tijsen et al25 showed circulating miR-423-5p as a potential biomarker of heart failure. Patients were recruited from a dyspnea registry, and interestingly, the level of miR-423-5p distinguished between dyspnea due to heart failure and dyspnea without heart failure. Circulating miRNA-423-5p correlated with N-terminal prohormone brain natriuretic peptide levels and ejection fraction. Indeed, miR423-5p was specifically enriched in the blood of heart failure cases, and receiver operator characteristic curve analysis showed miR423-5p to be a diagnostic predictor of heart failure. Another study found a significant increase in miR-499 levels in patients with acute heart failure, whereas no changes were found in diastolic heart failure.33 In patients with viral myocarditis, mild elevation of miR-208b and miR-499 was found.33Circulating miRNAs in Animal Models of Cardiovascular DiseaseCirculating miRNAs also have been evaluated in different animal models of heart disease. Isoproterenol treatment in rats induced myocardial injury and resulted in increased circulating miR-208 levels.26 In contrast, miR-208 levels remain unaffected in renal infarction models, thoracotomy surgery, or cardiac hypertrophy, demonstrating use as a potential and specific biomarker for myocardial injury.26 Upregulation of miR-208 levels also was reported by Wang et al32 and D'Alessandra et al24 in a model of coronary artery ligation in rats and mice, respectively. MiR-208a was elevated after 1 hour of left anterior descending coronary artery occlusion and reached a peak at 3 hours.32 Circulating miR-1 also was increased after myocardial infarction in animal models,24,30,32 and a positive correlation between infarct size and serum miR-1 levels after ischemia/reperfusion has been reported.30 In contrast to cardiac injury, miR-1, miR-133a, and miR-133b levels in mice with acute hind-limb ischemia were transiently reduced.24 Finally, miR-499-5p is increased after coronary artery ligation in mice, and levels closely correlate with TnI.24Limitations and Future DirectionsThe potential of selected circulating miRNAs or miRNA combinations to be used as specific biomarkers of distinct cardiovascular diseases is great. However, with few exceptions,29 the number of patients in the individual studies (Table) to date has been extremely low. It will be difficult to determine appropriate suitable endogenous controls because the expression profile of circulating miRNAs may change depending on the patient's cardiovascular disease state and medication. Finally, prognostic data for circulating miRNA levels in cardiovascular disease currently are lacking but may be available soon from several laboratories.ConclusionsMiRNAs emerge as potentially interesting and powerful new biomarkers for cardiovascular disease. Their role as paracrine signaling molecules in cardiovascular diseases remains to be determined.AcknowledgmentsWe thank Yvonne Görzig for preparation of the figure and editorial help.Sources of FundingThis work was funded by the Integriertes Forschungs-und Behandlungszentrum Transplantation and the Deutsche Forschungsgemeinschaft (TH903/7-2).DisclosuresDr Thum has filed patent applications for the use of miRNAs as therapeutics and biomarkers in cardiovascular disease.FootnotesMr Gupta and Ms Bang contributed equally to this article.Correspondence to Thomas Thum, MD, PhD, Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany. E-mail Thum.[email protected]deReferences1. Catalucci D, Gallo P, Condorelli G. MicroRNAs in cardiovascular biology and heart disease. Circ Cardiovasc Genet. 2009; 2:402–408.LinkGoogle Scholar2. Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007; 116:258–267.LinkGoogle Scholar3. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456:980–984.CrossrefMedlineGoogle Scholar4. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008; 141:672–675.CrossrefMedlineGoogle Scholar5. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9:654–659.CrossrefMedlineGoogle Scholar6. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, Nana-Sinkam SP, Jarjoura D, Marsh CB. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 2008; 3:e3694.CrossrefMedlineGoogle Scholar7. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Wurdinger T, Middeldorp JM. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010; 107:6328–6333.CrossrefMedlineGoogle Scholar8. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A. Serum microRNAs are promising novel biomarkers. PLoS One. 2008; 3:e3148.CrossrefMedlineGoogle Scholar9. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008; 105:10513–10518.CrossrefMedlineGoogle Scholar10. Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10:1470–1476.CrossrefMedlineGoogle Scholar11. Lee YS, Pressman S, Andress AP, Kim K, White JL, Cassidy JJ, Li X, Lubell K, Lim do H, Cho IS, Nakahara K, Preall JB, Bellare P, Sontheimer EJ, Carthew RW. Silencing by small RNAs is linked to endosomal trafficking. Nat Cell Biol. 2009; 11:1150–1156.CrossrefMedlineGoogle Scholar12. Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol. 2009; 11:1143–1149.CrossrefMedlineGoogle Scholar13. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010; 285:17442–17452.CrossrefMedlineGoogle Scholar14. Yuan A, Farber EL, Rapoport AL, Tejada D, Deniskin R, Akhmedov NB, Farber DB. Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One. 2009; 4:e4722.CrossrefMedlineGoogle Scholar15. Lai RC, Arslan F, Tan SS, Tan B, Choo A, Lee MM, Chen TS, Teh BJ, Eng JK, Sidik H, Tanavde V, Hwang WS, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Tan KH, Lim SK. Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles. J Mol Cell Cardiol. 2010; 48:1215–1224.CrossrefMedlineGoogle Scholar16. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010; 4:214–222.CrossrefMedlineGoogle Scholar17. Vrijsen KR, Sluijter JP, Schuchardt MW, van Balkom BW, Noort WA, Chamuleau SA, Doevendans PA. Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells. J Cell Mol Med. 2010; 14:1064–1070.MedlineGoogle Scholar18. Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, Li K, Yu B, Li Z, Wang R, Wang L, Li Q, Wang N, Shan H, Li Z, Yang B. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun. 2010; 391:73–77.CrossrefMedlineGoogle Scholar19. Wang K, Zhang S, Weber J, Baxter D, Galas DJ. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 2010. [Epub ahead of print]CrossrefGoogle Scholar20. Janowska-Wieczorek A, Majka M, Kijowski J, Baj-Krzyworzeka M, Reca R, Turner AR, Ratajczak J, Emerson SG, Kowalska MA, Ratajczak MZ. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood. 2001; 98:3143–3149.CrossrefMedlineGoogle Scholar21. Morel O, Toti F, Hugel B, Freyssinet JM. Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol. 2004; 11:156–164.CrossrefMedlineGoogle Scholar22. Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009; 19:43–51.CrossrefMedlineGoogle Scholar23. Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010; 50:298–301.CrossrefMedlineGoogle Scholar24. D'Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, Rubino M, Carena MC, Spazzafumo L, De Simone M, Micheli B, Biglioli P, Achilli F, Martelli F, Maggiolini S, Marenzi G, Pompilio G, Capogrossi MC. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J. 2010. [Epub ahead of print]CrossrefMedlineGoogle Scholar25. Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010; 106:1035–1039.LinkGoogle Scholar26. Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem. 2009; 55:1944–1949.CrossrefMedlineGoogle Scholar27. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010. [Epub ahead of print]CrossrefGoogle Scholar28. Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Roxe T, Muller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010; 107:677–684.LinkGoogle Scholar29. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010; 107:810–817.LinkGoogle Scholar30. Cheng Y, Tan N, Yang J, Liu X, Cao X, He P, Dong X, Qin S, Zhang C. A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond). 2010; 119:87–95.CrossrefMedlineGoogle Scholar31. Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y, Nonogi H, Iwai N. Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem. 2010; 56:1183–1185.CrossrefMedlineGoogle Scholar32. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010; 31:659–666.CrossrefMedlineGoogle Scholar33. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen J, Heymans S, Schroen B. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. In press.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ellison T, Stice S and Yao Y (2023) Therapeutic and diagnostic potential of extracellular vesicles in amyotrophic lateral sclerosis, Extracellular Vesicle, 10.1016/j.vesic.2022.100019, 2, (100019), Online publication date: 1-Dec-2023. Toor S, Aldous E, Parray A, Akhtar N, Al-Sarraj Y, Abdelalim E, Arredouani A, El-Agnaf O, Thornalley P, Pananchikkal S, Pir G, Ayadathil R, Shuaib A, Alajez N and Albagha O (2022) Circulating MicroRNA Profiling Identifies Distinct MicroRNA Signatures in Acute Ischemic Stroke and Transient Ischemic Attack Patients, International Journal of Molecular Sciences, 10.3390/ijms24010108, 24:1, (108) Waleczek F, Sansonetti M, Xiao K, Jung M, Mitzka S, Dendorfer A, Weber N, Perbellini F and Thum T (2022) Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model, Basic Research in Cardiology, 10.1007/s00395-022-00971-2, 117:1, Online publication date: 1-Dec-2022. Parvan R, Hosseinpour M, Moradi Y, Devaux Y, Cataliotti A and da Silva G (2022) Diagnostic performance of microRNAs in the detection of heart failure with reduced or preserved ejection fraction: a systematic review and meta‐analysis , European Journal of Heart Failure, 10.1002/ejhf.2700, 24:12, (2212-2225), Online publication date: 1-Dec-2022. Del Buono M, La Vecchia G, Rinaldi R, Sanna T, Crea F and Montone R (2022) Myocardial infarction with nonobstructive coronary arteries: the need for precision medicine, Current Opinion in Cardiology, 10.1097/HCO.0000000000000998, 37:6, (481-487), Online publication date: 1-Nov-2022. Saini V, Liu K, Surve A, Gupta S and Gupta A (2022) MicroRNAs as biomarkers for monitoring cardiovascular changes in Type II Diabetes Mellitus (T2DM) and exercise, Journal of Diabetes & Metabolic Disorders, 10.1007/s40200-022-01066-4, 21:2, (1819-1832) Mosallaei M, Ehtesham N, Rahimirad S, Saghi M, Vatandoost N and Khosravi S (2020) PBMCs: a new source of diagnostic and prognostic biomarkers, Archives of Physiology and Biochemistry, 10.1080/13813455.2020.1752257, 128:4, (1081-1087), Online publication date: 4-Jul-2022. Mun D, Kim H, Kang J, Yun N, Youn Y and Joung B (2022) Small extracellular vesicles derived from patients with persistent atrial fibrillation exacerbate arrhythmogenesis via miR-30a-5p, Clinical Science, 10.1042/CS20211141, 136:8, (621-637), Online publication date: 29-Apr-2022. Ntelios D, Georgiou E, Alexouda S, Malousi A, Efthimiadis G and Tzimagiorgis G (2021) A critical approach for successful use of circulating microRNAs as biomarkers in cardiovascular diseases: the case of hypertrophic cardiomyopathy, Heart Failure Reviews, 10.1007/s10741-021-10084-y, 27:1, (281-294), Online publication date: 1-Jan-2022. Niehof M, Reamon-Buettner S, Danov O, Hansen T and Sewald K (2021) A modified protocol for successful miRNA profiling in human precision-cut lung slices (PCLS), BMC Research Notes, 10.1186/s13104-021-05674-w, 14:1, Online publication date: 1-Dec-2021. Coban N, Ozuynuk A, Erkan A, Guclu-Geyik F and Ekici B (2021) Levels of miR-130b-5p in peripheral blood are associated with severity of coronary artery disease, Molecular Biology Reports, 10.1007/s11033-021-06780-5, 48:12, (7719-7732), Online publication date: 1-Dec-2021. Ferradini V, Vacca D, Belmonte B, Mango R, Scola L, Novelli G, Balistreri C and Sangiuolo F (2021) Genetic and Epigenetic Factors of Takotsubo Syndrome: A Systematic Review, International Journal of Molecular Sciences, 10.3390/ijms22189875, 22:18, (9875) Zhang W, Tian Z, Yang S, Rich J, Zhao S, Klingeborn M, Huang P, Li Z, Stout A, Murphy Q, Patz E, Zhang S, Liu G and Huang T (2021) Electrochemical micro-aptasensors for exosome detection based on hybridization chain reaction amplification, Microsystems & Nanoengineering, 10.1038/s41378-021-002
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