miRNAs as biomarkers of myocardial infarction: a step forward towards personalized medicine?

miRNAs are small noncoding RNAs known to post-transcriptionally regulate gene expression. miRNAs are expressed in the heart where they regulate multiple pathophysiological processes. The discovery of stable cardiac miRNAs in the bloodstream has also motivated the investigation of their potential as biomarkers. This review gathers the current knowledge on the use of miRNAs as novel biomarkers to improve risk stratification, diagnosis, and prognosis of patients with myocardial infarction. In the rapidly evolving era of biomarkers, the potential of miRNAs as promising tools to move personalized medicine a step forward is discussed.

[1]  Stefanie Dimmeler,et al.  Circulating MicroRNAs in Patients With Coronary Artery Disease , 2010, Circulation research.

[2]  Chunxiang Zhang,et al.  A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. , 2010, Clinical science.

[3]  Blake N Johnson,et al.  Biosensor-based microRNA detection: techniques, design, performance, and challenges. , 2014, The Analyst.

[4]  T. Rabelink,et al.  Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. , 2013, European heart journal.

[5]  K. Vickers,et al.  MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins , 2011, Nature Cell Biology.

[6]  Bin Zhou,et al.  Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[7]  O. Girard,et al.  Changes in circulating microRNAs levels with exercise modality. , 2013, Journal of applied physiology.

[8]  D. Barnett,et al.  Profile of plasma N-terminal proBNP following acute myocardial infarction; correlation with left ventricular systolic dysfunction. , 2000, European heart journal.

[9]  John McAnally,et al.  The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. , 2008, Developmental cell.

[10]  Kang Li,et al.  Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. , 2010, Biochemical and biophysical research communications.

[11]  Praveen Sethupathy,et al.  Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. , 2007, American journal of human genetics.

[12]  I. Komuro,et al.  A subset of circulating microRNAs are predictive for cardiac death after discharge for acute myocardial infarction. , 2012, Biochemical and biophysical research communications.

[13]  Shunsuke Noguchi,et al.  Microvesicle-mediated RNA molecule delivery system using monocytes/macrophages. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[14]  H. Nonogi,et al.  Assessment of plasma miRNAs in congestive heart failure. , 2011, Circulation journal : official journal of the Japanese Circulation Society.

[15]  A. Jaffe,et al.  Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T. , 2011, Journal of the American College of Cardiology.

[16]  Thomas J. Wang,et al.  Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training , 2011, The Journal of physiology.

[17]  F. Azuaje,et al.  Use of circulating microRNAs to diagnose acute myocardial infarction. , 2012, Clinical chemistry.

[18]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[19]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[20]  Yue Li,et al.  Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. , 2010, European heart journal.

[21]  G. Zhao,et al.  The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding. , 2013, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[22]  K. Vickers,et al.  Intercellular transport of microRNAs. , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[23]  D. Karolina,et al.  Circulating miRNA profiles in patients with metabolic syndrome. , 2012, The Journal of clinical endocrinology and metabolism.

[24]  Yvonne Tay,et al.  MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation , 2009, Nature.

[25]  AnnaZampetaki,et al.  Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes , 2010 .

[26]  Shiping Fang,et al.  Attomole microarray detection of microRNAs by nanoparticle-amplified SPR imaging measurements of surface polyadenylation reactions. , 2006, Journal of the American Chemical Society.

[27]  Y. Devaux,et al.  Association between circulating microRNAs, cardiovascular risk factors and outcome in patients with acute myocardial infarction. , 2013, International journal of cardiology.

[28]  Kunihiro Nishimura,et al.  Plasma microRNA 499 as a biomarker of acute myocardial infarction. , 2010, Clinical chemistry.

[29]  Min Xu,et al.  Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study , 2011, Acta Diabetologica.

[30]  Yariv Yogev,et al.  Serum MicroRNAs Are Promising Novel Biomarkers , 2008, PloS one.

[31]  M. Capogrossi,et al.  Admission levels of circulating miR-499-5p and risk of death in elderly patients after acute non-ST elevation myocardial infarction. , 2014, International journal of cardiology.

[32]  Toshihiro Tamura,et al.  Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients With Cardiovascular Disease Indicate Myocardial Damage , 2011, Circulation. Cardiovascular genetics.

[33]  A. Tijsen,et al.  Coronary Artery Disease CAD is caused by atherosclerosis of the coronary arteries , 2012 .

[34]  Á. Avezum,et al.  Predictors of hospital mortality in the global registry of acute coronary events. , 2003, Archives of internal medicine.

[35]  M. Hristov,et al.  Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection , 2009, Science Signaling.

[36]  B. Al-Lazikani,et al.  Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance , 2012, Clinical pharmacology and therapeutics.

[37]  Zhiqiang Gao,et al.  A microfluidic-assisted microarray for ultrasensitive detection of miRNA under an optical microscope. , 2011, Lab on a chip.

[38]  D. Erlinge,et al.  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 , 2011, Cardiology.

[39]  P. Doevendans,et al.  Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs , 2012, EMBO molecular medicine.

[40]  A. Tijsen,et al.  Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? , 2012, Circulation research.

[41]  Xueqing Yu,et al.  Signature microRNA Expression Profile of Essential Hypertension and Its Novel Link to Human Cytomegalovirus Infection , 2011, Circulation.

[42]  Hugo A. Katus,et al.  MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction , 2010, Basic Research in Cardiology.

[43]  U. A. Ørom,et al.  MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. , 2008, Molecular cell.

[44]  I. Komuro,et al.  Circulating p53-Responsive MicroRNAs Are Predictive Indicators of Heart Failure After Acute Myocardial Infarction , 2013, Circulation research.

[45]  G. Ma,et al.  Polymorphisms of miRNAs genes are associated with the risk and prognosis of coronary artery disease , 2012, Clinical Research in Cardiology.

[46]  Lu Zhang,et al.  MicroRNA-150: A Novel Marker of Left Ventricular Remodeling After Acute Myocardial Infarction , 2013, Circulation. Cardiovascular genetics.

[47]  M. Gladka,et al.  Small changes can make a big difference - microRNA regulation of cardiac hypertrophy. , 2012, Journal of molecular and cellular cardiology.

[48]  M. Mayr,et al.  Impact of intravenous heparin on quantification of circulating microRNAs in patients with coronary artery disease , 2013, Thrombosis and Haemostasis.

[49]  T. Tuschl,et al.  Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers , 2014, Proceedings of the National Academy of Sciences.

[50]  Y. Devaux,et al.  A Panel of 4 microRNAs Facilitates the Prediction of Left Ventricular Contractility after Acute Myocardial Infarction , 2013, PloS one.

[51]  J. Smith,et al.  Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction , 2013, BMC Cardiovascular Disorders.

[52]  D. Levy,et al.  Prediction of coronary heart disease using risk factor categories. , 1998, Circulation.

[53]  M. Zile,et al.  Relationship Between the Temporal Profile of Plasma microRNA and Left Ventricular Remodeling in Patients After Myocardial Infarction , 2011, Circulation. Cardiovascular genetics.

[54]  Huangxian Ju,et al.  Trace and label-free microRNA detection using oligonucleotide encapsulated silver nanoclusters as probes. , 2012, Analytical chemistry.

[55]  T. Fukami,et al.  Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects. , 2013, Toxicology and applied pharmacology.

[56]  G. Nuovo,et al.  MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. , 2009, Cardiovascular research.

[57]  Zhijian Yang,et al.  Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease , 2012, Lipids in Health and Disease.

[58]  Hugh S Markus,et al.  Circulating MicroRNAs as Novel Biomarkers for Platelet Activation , 2013, Circulation research.

[59]  S. Blankenberg,et al.  Assessment of microRNAs in patients with unstable angina pectoris. , 2014, European heart journal.

[60]  G. Condorelli,et al.  Deregulation of microRNA-503 Contributes to Diabetes Mellitus–Induced Impairment of Endothelial Function and Reparative Angiogenesis After Limb Ischemia , 2011, Circulation.

[61]  Holger Thiele,et al.  Relation of circulating MicroRNA-133a concentrations with myocardial damage and clinical prognosis in ST-elevation myocardial infarction. , 2012, American heart journal.

[62]  Keith W. Jones,et al.  Impact of Cellular miRNAs on Circulating miRNA Biomarker Signatures , 2011, PloS one.

[63]  A. Hata.  Functions of microRNAs in cardiovascular biology and disease. , 2013, Annual review of physiology.

[64]  S. Fujii,et al.  Circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol , 2012, Thrombosis Journal.

[65]  Raj Mutharasan,et al.  Sample preparation-free, real-time detection of microRNA in human serum using piezoelectric cantilever biosensors at attomole level. , 2012, Analytical chemistry.

[66]  J. Bauersachs,et al.  Biogenesis and Regulation of Cardiovascular MicroRNAs , 2011, Circulation Research.

[67]  G. Dorn,et al.  A Human 3′ miR-499 Mutation Alters Cardiac mRNA Targeting and Function , 2012, Circulation research.

[68]  Federica Limana,et al.  Circulating microRNAs are new and sensitive biomarkers of myocardial infarction , 2010, European heart journal.

[69]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[70]  J. Bauersachs,et al.  Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. , 2011, Journal of molecular and cellular cardiology.

[71]  G. Condorelli,et al.  Circulating MicroRNAs and Aerobic Fitness – The HUNT-Study , 2013, PloS one.

[72]  Z. Massy,et al.  miR-223: An inflammatory oncomiR enters the cardiovascular field. , 2014, Biochimica et biophysica acta.

[73]  M. Zile,et al.  Relationship Between The Temporal Profile of Plasma microRNA and Left Ventricular Remodeling In Patients Following Myocardial Infarction Running title : Zile , 2011 .

[74]  D. Atar,et al.  ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation , 2013 .

[75]  Florian Caiment,et al.  A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep , 2006, Nature Genetics.

[76]  Gang Wang,et al.  Comparing the diagnostic values of circulating microRNAs and cardiac troponin T in patients with acute myocardial infarction , 2013, Clinics.

[77]  Fred S Apple,et al.  Third universal definition of myocardial infarction , 2012 .

[78]  Wei Gao,et al.  Altered expression of microRNAs in the myocardium of rats with acute myocardial infarction , 2010, BMC cardiovascular disorders.

[79]  Y. Devaux,et al.  Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain , 2015, Journal of internal medicine.

[80]  Yingdong Zhao,et al.  Strengths and Limitations of Laboratory Procedures for MicroRNA Detection , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[81]  Thomas Thum,et al.  Non-coding RNAs in cardiac remodeling and heart failure. , 2013, Circulation research.

[82]  R. Testa,et al.  Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. , 2013, International journal of cardiology.

[83]  Tamas Dalmay,et al.  Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss , 2009, Nature Genetics.

[84]  Gozoh Tsujimoto,et al.  Intra-Platform Repeatability and Inter-Platform Comparability of MicroRNA Microarray Technology , 2009, PloS one.

[85]  J. Pu,et al.  Circulating microRNAs are promising novel biomarkers of acute myocardial infarction. , 2011, Internal medicine.

[86]  E. Kroh,et al.  Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma , 2011, Proceedings of the National Academy of Sciences.

[87]  Yanrui Li,et al.  miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1 , 2011, Nature Medicine.

[88]  I. Karakikes,et al.  Therapeutic Cardiac‐Targeted Delivery of miR‐1 Reverses Pressure Overload–Induced Cardiac Hypertrophy and Attenuates Pathological Remodeling , 2013, Journal of the American Heart Association.

[89]  Jan A Staessen,et al.  Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease , 2010, Circulation. Cardiovascular genetics.

[90]  T. Boettger,et al.  miR-1/133a Clusters Cooperatively Specify the Cardiomyogenic Lineage by Adjustment of Myocardin Levels during Embryonic Heart Development , 2013, PLoS genetics.