Abstract
MicroRNAs, key regulators of biological processes, are involved in the pathophysiological mechanisms underlying human diseases, including cardiovascular diseases. Their recent discovery revealed a previously unknown layer of pathophysiologic regulators, which also play a key role in the regulation of several aspects of cardiovascular diseases. More recently, it was demonstrated that circulating microRNAs can be measured in the blood. Hence, the potential use of microRNAs as disease biomarkers attracted many research groups. Indeed, their unusual stability in the bloodstream and during prolonged storage make circulating miRs very interesting as potential biomarkers. Circulating microRNAs are emerging as the next generation “smart” biomarkers and could be helpful in further improving the diagnostic and therapeutic processes of cardiovascular diseases. The present chapter summarizes the most relevant experimental evidence on circulating microRNAs in cardiovascular diseases, including arterial remodeling, restenosis, coronary artery disease, acute coronary syndromes, hypertension, heart failure, and ischemic stroke, highlighting potential pathophysiological correlations to the mechanisms underlying cardiovascular diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Ai J, Zhang R, Li Y et al (2010) Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 391:73–77
Arroyo JD, Chevillet JR, Kroh EM et al (2011) Argonaute2 complexes carry a population of circulating miRs independent of vesicles in human plasma. Proc Natl Acad Sci USA 108:5003–5008
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Bostjancic E, Zidar N, Stajer D et al (2010) MiRs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human myocardial infarction. Cardiology 115:163–169
Casscells W (1992) Migration of smooth muscle and endothelial cells. Critical events in restenosis. Circulation 86:723–729
Cheng Y, Tan N, Yang J et al (2010) A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci 119:87–95
Cirillo P, Golino P, Calabrò P (2003) Activated platelets stimulate tissue factor expression in smooth muscle cells. Thromb Res 112:51–57
Corsten MF, Dennert R, Jochems S et al (2010) Circulating MicroRNA-208b and MicroRNA 499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3:499–506
Curcio A, Torella D, Iaconetti C et al (2013) MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts. PLoS ONE 8, e70158
D’Alessandra Y, Devanna P, Limana F et al (2010) Circulating miRs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 31:2765–2773
De Rosa S, Fichtlscherer S, Lehmann R et al (2011) Transcoronary concentration gradients of circulating miRs. Circulation 124:1936–1944
De Rosa S, Curcio A, Indolfi C (2014) Emerging role of microRNAs in cardiovascular diseases. Circ J 78:567–575
Devaux Y, Vausort M, Goretti E et al (2012) Use of circulating miRs to diagnose acute myocardial infarction. Clin Chem 58:559–567
Devaux Y, Vausort M, McCann GP et al (2013) A panel of 4 microRNAs facilitates the prediction of left ventricular contractility after acute myocardial infarction. PLoS ONE 8, e70644
Devaux Y, Mueller M, Haaf P et al (2015) Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain. J Intern Med 277:260–271
Dharap A, Bowen K, Place R et al (2009) Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab 29:675–687
Dong S, Cheng Y, Yang J et al (2009) MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction. J Biol Chem 284:29514–29525
Edelstein LC, Bray PF (2011) MicroRNAs in platelet production and activation. Blood 117:5289–5296
Eskildsen TV, Jeppesen PL, Schneider M et al (2013) Angiotensin II regulates microRNA-132/-212 in hypertensive rats and humans. Int J Mol Sci 14:11190–11207
Fichtlscherer S, De Rosa S, Fox H et al (2010) Circulating miRs in patients with coronary artery disease. Circ Res 107:677–684
Flammer AJ, Gössl M, Widmer RJ et al (2012) Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis. Eur Heart J 33:2963–2969
Fukushima Y, Nakanishi M, Nonogi H et al (2011) Assessment of plasma miRs in congestive heart failure. Circ J 75:336–340
Gidlof O, Andersson P, van der Pals J et al (2011) 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. Cardiology 118:217–226
Goren Y, Kushnir M, Zafrir B et al (2012) Serum levels of miRs in patients with heart failure. Eur Heart Fail 14:147–154
He M, Gong Y, Shi J et al (2014a) Plasma microRNAs as potential noninvasive biomarkers for in-stent restenosis. PLoS ONE 9, e112043
He F, Lv P, Zhao X et al (2014b) Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction. Mol Cell Biochem 394:137–144
Hergenreider E, Heydt S, Tréguer K et al (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14:249–256
Iaconetti C, Polimeni A, Sorrentino S et al (2012) Inhibition of mir-92a increases endothelial proliferation and migration in vitro as well as reduces neointimal proliferation in vivo after vascular injury. Basic Res Cardiol 107:296–309
Iaconetti C, Gareri C, Polimeni A et al (2013) Non-coding RNAs: the “dark matter” of cardiovascular pathophysiology. Int J Mol Sci 14:19987–20018
Iaconetti C, De Rosa S, Polimeni A et al (2015) Down-regulation of miR-23b induces phenotypic switching of vascular smooth muscle cells in vitro and in vivo. Cardiovasc Res 107(4):522–533, pii: cvv141
Ikitimur B, Cakmak HA, Coskunpinar E et al (2015) Relationship between circulating microRNAs and left ventricular mass in symptomatic heart failure patients with systolic dysfunction. Kardiol Pol. doi:10.5603/KP.a2015.0082 [Epub ahead of print]
Indolfi C, Curcio A (2014) Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy. J Clin Invest 124:1896–1898
Indolfi C, Avvedimento EV, Rapacciuolo A et al (1995) Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo. Nat Med 1:541–545
Indolfi C, Di Lorenzo E, Rapacciuolo A et al (2000) 8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima forma- tion induced by balloon injury in vivo. J Am Coll Cardiol 36:288–293
Indolfi C, Torella D, Cavuto L et al (2001) Effects of balloon injury on neointimal hyperplasia in streptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats. Circulation 103:2980–2986
Indolfi C, Torella D, Coppola C et al (2002) Rat carotid artery dilation by PTCA balloon catheter induces neointima formation in presence of IEL rupture. Am J Physiol Heart Circ Physiol 283:H760–H767
Indolfi C, Mongiardo A, Curcio A et al (2003) Molecular mechanisms of in-stent restenosis and approach to therapy with eluting stents. Trends Cardiovasc Med 13:142–148
Indolfi C, Gasparri C, Vicinanza C et al (2011) Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes. Basic Res Cardiol 106:667–679
Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966
Ji X, Takahashi R, Hiura Y et al (2009) Plasma miR-208 as a biomarker of myocardial injury. Clin Chem 55:1944–1949
Kim JM, Jung KH, Chu K et al (2015) Atherosclerosis-related circulating microRNAs as a predictor of stroke recurrence. Transl Stroke Res 6:191–197
Kondkar AA, Bray MS, Leal SM et al (2010) VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 8:369–378
Kontaraki JE, Marketou ME, Zacharis EA et al (2014) MicroRNA-9 and microRNA-126 expression levels in patients with essential hypertension: potential markers of target-organ damage. J Am Soc Hypertens 8:368–375
Landry P, Plante I, Ouellet DL et al (2009) Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 16:961–966
Laterza OF, Lim L, Garrett-Engele PW et al (2009) Plasma MiRs as sensitive and specific biomarkers of tissue injury. Clin Chem 55:1977–1983
Leistner DM, Fichtlscherer S, Thome C et al (2013) OCT-derived coronary plaque morphology and transcoronary concentration gradients of vessel wall-associated microRNAs. Eur Heart J 34(suppl 1). doi:10.1093/eurheartj/eht310.P5445
Li P, Teng F, Gao F et al (2015) Identification of circulating microRNAs as potential biomarkers for detecting acute ischemic stroke. Cell Mol Neurobiol 35:433–447
Liu DZ, Tian Y, Ander BP et al (2010) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101
Marques FZ, Campain AE, Tomaszewski M (2011) Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. Hypertension 58:1093–1098
Meder B, Keller A, Vogel B et al (2011) MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol 106:13–23
Meyer SU, Kaiser S, Wagner C et al (2012) Profound effect of profiling platform and normalization strategy on detection of differentially expressed microRNAs--a comparative study. PLoS ONE 7, e38946
Monleau M, Bonnel S, Gostan T et al (2014) Comparison of different extraction techniques to profile microRNAs from human sera and peripheral blood mononuclear cells. BMC Genomics 15:395
Moon JH, Chae MK, Kim KJ et al (2012) Decreased endothelial progenitor cells and increased serum glycated albumin are independently correlated with plaque-forming carotid artery atherosclerosis in type 2 diabetes patients without documented ischemic disease. Circ J 76:2273–2279
Nagalla S, Shaw C, Kong X et al (2011) Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 117:5189–5197
Olivieri F, Antonicelli R, Lorenzi M et al (2013) Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. Int J Cardiol 167:531–536
Polimeni A, De Rosa S, Indolfi C (2013) Vascular miRNAs after balloon angioplasty. Trends Cardiovasc Med 23:9–14
Qureshi IA, Mehler MF (2010) The emerging role of epigenetics in stroke: II. RNA regulatory circuitry. Arch Neurol 67:1435–1441
Rayner KJ, Moore KJ (2014) MicroRNA control of high-density lipoprotein metabolism and function. Circ Res 114:183–192
Ren J, Zhang J, Xu N et al (2013) Signature of circulating microRNAs as potential biomarkers in vulnerable coronary artery disease. PLoS ONE 8, e80738
Rink C, Khanna S (2011) MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics 43:521–528
Rixe J, Rolf A, Fichtlscherer S et al (2011) Plasma levels of circulating microRNAs correlate with coronary plaque burden as assessed by cardiac computed tomography. Circulation 124:1. (Abstract 15162)
Sanchis J, Bardají A, Bosch X et al (2012) Usefulness of high-sensitivity troponin T for the evaluation of patients with acute chest pain and no or minimal myocardial damage. Am Heart J 164:194–200
Santovito D, Mandolini C, Marcantonio P et al (2013) Overexpression of microRNA-145 in atherosclerotic plaques from hypertensive patients. Expert Opin Ther Targets 17:217–223
Sondermeijer BM, Bakker A, Halliani A et al (2011) Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340 and miRNA624. PLoS ONE 6, e25946
Stellos K, Dimmeler S (2014) Vascular MicroRNAs: from disease mechanisms to therapeutic targets. Circ Res 114:3–4
Tan KS, Armugam A, Sepramaniam S et al (2009) Expression profile of MiRs in young stroke patients. PLoS ONE 4, e7689
Tijsen AJ, Creemers EE, Moerland PD et al (2010) MiR423-5p as a circulating biomarker for heart failure. Circ Res 106:1035–1039
Torella D, Iaconetti C, Catalucci D et al (2011) MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo. Circ Res 109:880–893
Turchinovich A, Weiz L, Langheinz A et al (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res 39:7223–7233
Voellenkle C, van Rooij J, Cappuzzello C et al (2010) MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genomics 42:420–426
Wang GK, Zhu JQ, Zhang JT et al (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31:659–666
Wang R, Li N, Zhang Y et al (2011) Circulating MiRs are promising novel biomarkers of acute myocardial infarction. Intern Med 50:1789–1795
Widera C, Gupta SK, Lorenzen JM et al (2011) Diagnostic and prognosticimpact of six circulating miRs in acute coronary syndrome. J Mol Cell Cardiol 51:872–875
Willerson JT, Golino P, Eidt J et al (1989) Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications. Circulation 80:198–205
Wong LL, Armugam A, Sepramaniam S et al (2015) Circulating microRNAs in heart failure with reduced and preserved left ventricular ejection fraction. Eur J Heart Fail 17:393–404
Xiao J, Jing ZC, Ellinor PT et al (2011) MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute pulmonary embolism. J Transl Med 9:159
Zeng L, Liu J, Wang Y (2011) MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia. Front Biosci 3:1265–1272
Zhang Y, Liu D, Chen X et al (2010) Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell 39:133–144
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
De Rosa, S., Indolfi, C. (2015). Circulating microRNAs as Biomarkers in Cardiovascular Diseases. In: Igaz, P. (eds) Circulating microRNAs in Disease Diagnostics and their Potential Biological Relevance. Experientia Supplementum, vol 106. Springer, Basel. https://doi.org/10.1007/978-3-0348-0955-9_6
Download citation
DOI: https://doi.org/10.1007/978-3-0348-0955-9_6
Published:
Publisher Name: Springer, Basel
Print ISBN: 978-3-0348-0953-5
Online ISBN: 978-3-0348-0955-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)