Circulating miRNA as novel markers for diastolic dysfunction
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Circulating miRNA as novel markers for diastolic dysfunction Nandini Nair • Sandeep Kumar • Enrique Gongora Sudhiranjan Gupta
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Received: 16 August 2012 / Accepted: 6 December 2012 / Published online: 18 December 2012 Ó Springer Science+Business Media New York 2012
Abstract MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. Though their significance is unclear, pioneer profiling studies have attributed specific serum miRNA signatures to different disease conditions. The diagnostic potential of miRNA detection in human plasma for cardiovascular disorders is beginning to be recognized as important. In this study, we examined miRNA profiling in isolated diastolic dysfunction (DD) with preserved systolic function to identify promising candidate miRNAs. The presence of these miRNAs was tested in stable patients with isolated DD, patients with stable compensated dilated cardiomyopathy (DCM—systolic plus diastolic dysfunction) and those with decompensated congestive heart failure secondary to dilated cardiomyopathy (DCM–CHF—systolic plus diastolic dysfunction). We identified new circulating miRNAs (miR454, miR-500, miR-1246, miR-142-3p) which showed
distinct patterns of expression in patients with diastolic dysfunction. The presence or absence of systolic dysfunction does not seem to affect this trend. MiR-454 and miR500 are downregulated in diastolic dysfunction. MiR-1246 is upregulated in diastolic dysfunction. MiR-142-3p is downregulated in DCM and DCM–CHF groups but not in the DD group. The expression of miR-124-5p is highly upregulated in DCM but not in DD and DCM–CHF groups. We therefore propose that these circulating miRNAs may serve as novel biomarkers for diastolic dysfunction because in all of these patients the only common factor was diastolic dysfunction. Keywords Diastolic dysfunction MicroRNA profiling Biomarker panel
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s11010-012-1546-x) contains supplementary material, which is available to authorized users. N. Nair (&) E. Gongora Scott & White Memorial Hospital/TAMHSC College of Medicine, Temple, TX 76508, USA e-mail: [email protected] S. Kumar S. Gupta (&) Department of Medicine, Division of Molecular Cardiology, Texas A&M Health Science Center, Scott & White, Central Texas Veterans Health Care System, College of Medicine, Temple, TX 76504, USA e-mail: [email protected] Present Address: E. Gongora Drexel University College of Medicine, Mail Stop 111, 245 North Broad Street, Philadelphia, PA 19102, USA
MicroRNAs (miRNAs) are small (&21 nucleotides) noncoding RNAs that negatively regulate gene expression by binding to the 30 -UTR sites in the messenger RNAs of protein-coding genes and downregulate their protein expression [1]. Their critical patho-physiological importance is evidenced by their marked evolutionary conservation. Current estimates suggest that they fine-tune expression of up to 50 % of protein-coding genes [2, 3]. MiRNAs are crucial for virtua
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