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Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy

Authors: Lu Fang, Andris H. Ellims, Xiao-lei Moore, David A. White, Andrew J. Taylor, Jaye Chin-Dusting, Anthony M. Dart

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

Background

Circulating microRNAs may represent novel markers for cardiovascular diseases. We evaluated whether circulating miRNAs served as potential biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM).

Methods

Cardiac magnetic resonance imaging with postcontrast T1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T1 < 470 ms or T1 ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). First, we screened 84 miRNAs using human serum/plasma miRNA array on plasma of 8 HCM patients (4/group based on T1 time) and 4 healthy controls. From the results of this initial array, 16 miRNAs were selected based on their fold changes and relevance to myocardial fibrosis for further validation by Taqman real-time PCR in 55 HCM patients.

Results

Among the 16 miRNAs, the expression of miR-96-5p and miR-373-3p was low. The remaining 14 (miR-18a-5p, miR-146a-5p, miR-30d-5p, miR-17-5p, miR-200a-3p, miR-19b-3p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-192-5p, miR-296-5p, miR-29a-3p, and miR-133a-3p) were upregulated in HCM patients with T1 < 470 ms compared with those with T1 ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T1 values. Individual miRNA had moderate diagnostic value for diffuse myocardial fibrosis (AUC: 0.663–0.742), but the diagnostic value was greatly improved (AUC: 0.87) for a combination of 8 miRNAs. In comparison, circulating markers of collagen turnover did not have predictive values for diffuse myocardial fibrosis.

Conclusions

These findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.
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Literature
1.
go back to reference Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment. Circulation. 2002;105(12):1503–8.CrossRefPubMed Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment. Circulation. 2002;105(12):1503–8.CrossRefPubMed
2.
go back to reference Sabbah HN, Sharov VG, Lesch M, Goldstein S. Progression of heart failure: a role for interstitial fibrosis. Mol Cell Biochem. 1995;147(1–2):29–34.CrossRefPubMed Sabbah HN, Sharov VG, Lesch M, Goldstein S. Progression of heart failure: a role for interstitial fibrosis. Mol Cell Biochem. 1995;147(1–2):29–34.CrossRefPubMed
3.
go back to reference Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart. 2000;84(5):476–82.PubMedCentralCrossRefPubMed Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart. 2000;84(5):476–82.PubMedCentralCrossRefPubMed
4.
go back to reference Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36–44.CrossRefPubMed Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36–44.CrossRefPubMed
5.
go back to reference Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57(8):891–903.CrossRefPubMed Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57(8):891–903.CrossRefPubMed
6.
go back to reference Kim RJ, Judd RM. Gadolinium-enhanced magnetic resonance imaging in hypertrophic cardiomyopathy: in vivo imaging of the pathologic substrate for premature cardiac death? J Am Coll Cardiol. 2003;41(9):1568–72.CrossRefPubMed Kim RJ, Judd RM. Gadolinium-enhanced magnetic resonance imaging in hypertrophic cardiomyopathy: in vivo imaging of the pathologic substrate for premature cardiac death? J Am Coll Cardiol. 2003;41(9):1568–72.CrossRefPubMed
7.
go back to reference Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Kaye DM, Taylor AJ. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol. 2008;52(19):1574–80.CrossRefPubMed Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Kaye DM, Taylor AJ. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol. 2008;52(19):1574–80.CrossRefPubMed
8.
go back to reference Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122(2):138–44.CrossRefPubMed Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122(2):138–44.CrossRefPubMed
9.
go back to reference Chan W, Duffy SJ, White DA, Gao XM, Du XJ, Ellims AH, Dart AM, Taylor AJ. Acute left ventricular remodeling following myocardial infarction: coupling of regional healing with remote extracellular matrix expansion. JACC Cardiovasc Imaging. 2012;5(9):884–93.CrossRefPubMed Chan W, Duffy SJ, White DA, Gao XM, Du XJ, Ellims AH, Dart AM, Taylor AJ. Acute left ventricular remodeling following myocardial infarction: coupling of regional healing with remote extracellular matrix expansion. JACC Cardiovasc Imaging. 2012;5(9):884–93.CrossRefPubMed
10.
go back to reference Ling LH, Kistler PM, Ellims AH, Iles LM, Lee G, Hughes GL, Kalman JM, Kaye DM, Taylor AJ. Diffuse Ventricular fibrosis in atrial fibrillation: noninvasive evaluation and relationships with aging and systolic dysfunction. J Am Coll Cardiol. 2012;60:2402–8.CrossRefPubMed Ling LH, Kistler PM, Ellims AH, Iles LM, Lee G, Hughes GL, Kalman JM, Kaye DM, Taylor AJ. Diffuse Ventricular fibrosis in atrial fibrillation: noninvasive evaluation and relationships with aging and systolic dysfunction. J Am Coll Cardiol. 2012;60:2402–8.CrossRefPubMed
11.
go back to reference Ellims AH, Iles LM, Ling LH, Hare JL, Kaye DM, Taylor AJ. Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction. J Cardiovasc Magn Reson. 2012;14(1):76.PubMedCentralCrossRefPubMed Ellims AH, Iles LM, Ling LH, Hare JL, Kaye DM, Taylor AJ. Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction. J Cardiovasc Magn Reson. 2012;14(1):76.PubMedCentralCrossRefPubMed
12.
go back to reference Mascherbauer J, Marzluf BA, Tufaro C, Pfaffenberger S, Graf A, Wexberg P, Panzenbock A, Jakowitsch J, Bangert C, Laimer D, et al. Cardiac magnetic resonance postcontrast T1 time is associated with outcome in patients with heart failure and preserved ejection fraction. Circ Cardiovasc Imaging. 2013;6(6):1056–65.CrossRefPubMed Mascherbauer J, Marzluf BA, Tufaro C, Pfaffenberger S, Graf A, Wexberg P, Panzenbock A, Jakowitsch J, Bangert C, Laimer D, et al. Cardiac magnetic resonance postcontrast T1 time is associated with outcome in patients with heart failure and preserved ejection fraction. Circ Cardiovasc Imaging. 2013;6(6):1056–65.CrossRefPubMed
13.
go back to reference Sibley CT, Noureldin RA, Gai N, Nacif MS, Liu S, Turkbey EB, Mudd JO, van der Geest RJ, Lima JA, Halushka MK, et al. T1 mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy. Radiology. 2012;265(3):724–32.PubMedCentralCrossRefPubMed Sibley CT, Noureldin RA, Gai N, Nacif MS, Liu S, Turkbey EB, Mudd JO, van der Geest RJ, Lima JA, Halushka MK, et al. T1 mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy. Radiology. 2012;265(3):724–32.PubMedCentralCrossRefPubMed
14.
go back to reference Vickers KC, Rye KA, Tabet F. MicroRNAs in the onset and development of cardiovascular disease. Clin Sci Lond. 2014;126(3):183–94.CrossRefPubMed Vickers KC, Rye KA, Tabet F. MicroRNAs in the onset and development of cardiovascular disease. Clin Sci Lond. 2014;126(3):183–94.CrossRefPubMed
17.
go back to reference Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, Lo YM. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54(3):482–90.CrossRefPubMed Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, Lo YM. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54(3):482–90.CrossRefPubMed
18.
go back to reference Creemers EE, Tijsen AJ, Pinto YM. Circulating MicroRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–95.CrossRefPubMed Creemers EE, Tijsen AJ, Pinto YM. Circulating MicroRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–95.CrossRefPubMed
19.
go back to reference Fichtlscherer S, Zeiher AM, Dimmeler S. Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol. 2011;31(11):2383–90.CrossRefPubMed Fichtlscherer S, Zeiher AM, Dimmeler S. Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol. 2011;31(11):2383–90.CrossRefPubMed
20.
go back to reference Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH 3rd, Spirito P, Ten Cate FJ. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2003;42(9):1687–713.CrossRefPubMed Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH 3rd, Spirito P, Ten Cate FJ. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2003;42(9):1687–713.CrossRefPubMed
21.
go back to reference Fang L, Beale A, Ellims AH, Moore XL, Ling LH, Taylor AJ, Chin-Dusting J, Dart AM. Associations between fibrocytes and postcontrast myocardial T1 times in hypertrophic cardiomyopathy. J Am Heart Assoc. 2013;2(5):e000270.PubMedCentralCrossRefPubMed Fang L, Beale A, Ellims AH, Moore XL, Ling LH, Taylor AJ, Chin-Dusting J, Dart AM. Associations between fibrocytes and postcontrast myocardial T1 times in hypertrophic cardiomyopathy. J Am Heart Assoc. 2013;2(5):e000270.PubMedCentralCrossRefPubMed
22.
go back to reference Gai N, Turkbey EB, Nazarian S, van der Geest RJ, Liu CY, Lima JA, Bluemke DA. T1 mapping of the gadolinium-enhanced myocardium: adjustment for factors affecting interpatient comparison. Magn Reson Med. 2011;65(5):1407–15.PubMedCentralCrossRefPubMed Gai N, Turkbey EB, Nazarian S, van der Geest RJ, Liu CY, Lima JA, Bluemke DA. T1 mapping of the gadolinium-enhanced myocardium: adjustment for factors affecting interpatient comparison. Magn Reson Med. 2011;65(5):1407–15.PubMedCentralCrossRefPubMed
23.
go back to reference Querejeta R, Varo N, Lopez B, Larman M, Artinano E, Etayo JC, Martinez Ubago JL, Gutierrez-Stampa M, Emparanza JI, Gil MJ, et al. Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease. Circulation. 2000;101(14):1729–35.CrossRefPubMed Querejeta R, Varo N, Lopez B, Larman M, Artinano E, Etayo JC, Martinez Ubago JL, Gutierrez-Stampa M, Emparanza JI, Gil MJ, et al. Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease. Circulation. 2000;101(14):1729–35.CrossRefPubMed
24.
go back to reference Velagaleti RS, Gona P, Sundstrom J, Larson MG, Siwik D, Colucci WS, Benjamin EJ, Vasan RS. Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality. Arterioscler Thromb Vasc Biol. 2010;30(11):2283–8.PubMedCentralCrossRefPubMed Velagaleti RS, Gona P, Sundstrom J, Larson MG, Siwik D, Colucci WS, Benjamin EJ, Vasan RS. Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality. Arterioscler Thromb Vasc Biol. 2010;30(11):2283–8.PubMedCentralCrossRefPubMed
25.
go back to reference Kupari M, Laine M, Turto H, Lommi J, Werkkala K. Circulating collagen metabolites, myocardial fibrosis and heart failure in aortic valve stenosis. J Heart Valve Dis. 2013;22(2):166–76.PubMed Kupari M, Laine M, Turto H, Lommi J, Werkkala K. Circulating collagen metabolites, myocardial fibrosis and heart failure in aortic valve stenosis. J Heart Valve Dis. 2013;22(2):166–76.PubMed
26.
go back to reference Roncarati R, Viviani Anselmi C, Losi MA, Papa L, Cavarretta E, Da Costa Martins P, Contaldi C, Saccani Jotti G, Franzone A, Galastri L, et al. Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2014;63(9):920–7.CrossRefPubMed Roncarati R, Viviani Anselmi C, Losi MA, Papa L, Cavarretta E, Da Costa Martins P, Contaldi C, Saccani Jotti G, Franzone A, Galastri L, et al. Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2014;63(9):920–7.CrossRefPubMed
27.
go back to reference Ellims AH, Shaw JA, Stub D, Iles LM, Hare JL, Slavin GS, Kaye DM, Taylor AJ. Diffuse myocardial fibrosis evaluated by post-contrast t1 mapping correlates with left ventricular stiffness. J Am Coll Cardiol. 2014;63(11):1112–8.CrossRefPubMed Ellims AH, Shaw JA, Stub D, Iles LM, Hare JL, Slavin GS, Kaye DM, Taylor AJ. Diffuse myocardial fibrosis evaluated by post-contrast t1 mapping correlates with left ventricular stiffness. J Am Coll Cardiol. 2014;63(11):1112–8.CrossRefPubMed
28.
go back to reference Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980–4.CrossRefPubMed Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980–4.CrossRefPubMed
29.
go back to reference van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA. 2008;105(35):13027–32.PubMedCentralCrossRefPubMed van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA. 2008;105(35):13027–32.PubMedCentralCrossRefPubMed
30.
go back to reference Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I, Herias V, van Leeuwen RE, Schellings MW, Barenbrug P, et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009;104(2):170–8 (176p following 178).CrossRefPubMed Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I, Herias V, van Leeuwen RE, Schellings MW, Barenbrug P, et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009;104(2):170–8 (176p following 178).CrossRefPubMed
31.
go back to reference van Almen GC, Verhesen W, van Leeuwen RE, van de Vrie M, Eurlings C, Schellings MW, Swinnen M, Cleutjens JP, van Zandvoort MA, Heymans S, et al. MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure. Aging Cell. 2011;10(5):769–79.PubMedCentralCrossRefPubMed van Almen GC, Verhesen W, van Leeuwen RE, van de Vrie M, Eurlings C, Schellings MW, Swinnen M, Cleutjens JP, van Zandvoort MA, Heymans S, et al. MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure. Aging Cell. 2011;10(5):769–79.PubMedCentralCrossRefPubMed
32.
go back to reference Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, Jandeleit-Dahm K, Burns WC, Thomas MC, Cooper ME, et al. miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes. 2011;60(1):280–7.PubMedCentralCrossRefPubMed Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, Jandeleit-Dahm K, Burns WC, Thomas MC, Cooper ME, et al. miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes. 2011;60(1):280–7.PubMedCentralCrossRefPubMed
34.
go back to reference Han X, Yan S, Weijie Z, Feng W, Liuxing W, Mengquan L, Qingxia F. Critical role of miR-10b in transforming growth factor-beta1-induced epithelial-mesenchymal transition in breast cancer. Cancer Gene Ther. 2014;21(2):60–7.CrossRefPubMed Han X, Yan S, Weijie Z, Feng W, Liuxing W, Mengquan L, Qingxia F. Critical role of miR-10b in transforming growth factor-beta1-induced epithelial-mesenchymal transition in breast cancer. Cancer Gene Ther. 2014;21(2):60–7.CrossRefPubMed
35.
go back to reference Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, Natarajan R. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA. 2007;104(9):3432–7.PubMedCentralCrossRefPubMed Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, Natarajan R. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA. 2007;104(9):3432–7.PubMedCentralCrossRefPubMed
36.
go back to reference Sheedy FJ, O’Neill LA. Adding fuel to fire: microRNAs as a new class of mediators of inflammation. Ann Rheum Dis. 2008;67(Suppl 3):iii50–5.CrossRefPubMed Sheedy FJ, O’Neill LA. Adding fuel to fire: microRNAs as a new class of mediators of inflammation. Ann Rheum Dis. 2008;67(Suppl 3):iii50–5.CrossRefPubMed
37.
go back to reference Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103(33):12481–6.PubMedCentralCrossRefPubMed Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103(33):12481–6.PubMedCentralCrossRefPubMed
38.
go back to reference Guo CJ, Pan Q, Li DG, Sun H, Liu BW. miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: an essential role for apoptosis. J Hepatol. 2009;50(4):766–78.CrossRefPubMed Guo CJ, Pan Q, Li DG, Sun H, Liu BW. miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: an essential role for apoptosis. J Hepatol. 2009;50(4):766–78.CrossRefPubMed
39.
go back to reference Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008;14(5):382–93.PubMedCentralCrossRefPubMed Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008;14(5):382–93.PubMedCentralCrossRefPubMed
40.
go back to reference Tijsen AJ, Pinto YM, Creemers EE. Non-cardiomyocyte microRNAs in heart failure. Cardiovasc Res. 2012;93(4):573–82.CrossRefPubMed Tijsen AJ, Pinto YM, Creemers EE. Non-cardiomyocyte microRNAs in heart failure. Cardiovasc Res. 2012;93(4):573–82.CrossRefPubMed
41.
42.
go back to reference Feng B, Chen S, McArthur K, Wu Y, Sen S, Ding Q, Feldman RD, Chakrabarti S. miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes. 2011;60(11):2975–84.PubMedCentralCrossRefPubMed Feng B, Chen S, McArthur K, Wu Y, Sen S, Ding Q, Feldman RD, Chakrabarti S. miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes. 2011;60(11):2975–84.PubMedCentralCrossRefPubMed
43.
go back to reference Hecker M, Thamilarasan M, Koczan D, Schroder I, Flechtner K, Freiesleben S, Fullen G, Thiesen HJ, Zettl UK. MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci. 2013;14(8):16087–110.PubMedCentralCrossRefPubMed Hecker M, Thamilarasan M, Koczan D, Schroder I, Flechtner K, Freiesleben S, Fullen G, Thiesen HJ, Zettl UK. MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci. 2013;14(8):16087–110.PubMedCentralCrossRefPubMed
44.
go back to reference 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(6):654–9.CrossRefPubMed 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(6):654–9.CrossRefPubMed
Metadata
Title
Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy
Authors
Lu Fang
Andris H. Ellims
Xiao-lei Moore
David A. White
Andrew J. Taylor
Jaye Chin-Dusting
Anthony M. Dart
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0672-0

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