MicroRNA Expression Profile in CAD Patients and the Impact of ACEI/ARB

Coronary artery disease (CAD) is the largest killer of males and females in the United States. There is a need to develop innovative diagnostic markers for this disease. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in important cellular processes, and we hypothesized that the miRNA expression profile would be altered in whole blood samples of patients with CAD. We performed a microarray analysis on RNA from the blood of 5 male subjects with CAD and 5 healthy subjects (mean age 53 years). Subsequently, we performed qRT-PCR analysis of miRNA expression in whole blood of another 10 patients with CAD and 15 healthy subjects. We identified 11 miRNAs that were significantly downregulated in CAD subjects (P < .05). Furthermore, we found an association between ACEI/ARB use and downregulation of several miRNAs that was independent of the presence of significant CAD. In conclusion, we have identified a distinct miRNA signature in whole blood that discriminates CAD patients from healthy subjects. Importantly, medication use may significantly alter miRNA expression. These findings may have significant implications for identifying and managing individuals that either have CAD or are at risk of developing the disease.

[1]  T. V. van Berkel,et al.  The peripheral blood mononuclear cell microRNA signature of coronary artery disease. , 2010, Biochemical and biophysical research communications.

[2]  Geoffrey S Ginsburg,et al.  Correlation of Peripheral-Blood Gene Expression With the Extent of Coronary Artery Stenosis , 2008, Circulation. Cardiovascular genetics.

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

[4]  Pascal J. Goldschmidt-Clermont,et al.  Gene Expression Patterns in Peripheral Blood Correlate with the Extent of Coronary Artery Disease , 2009, PloS one.

[5]  R. Giugliano,et al.  Novel biomarkers in cardiovascular disease: update 2010. , 2010, American heart journal.

[6]  Junjie Xiao,et al.  Circulating microRNAs: novel biomarkers for cardiovascular diseases , 2011, Journal of Molecular Medicine.

[7]  Jan Krützfeldt,et al.  Strategies to determine the biological function of microRNAs , 2006, Nature Genetics.

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

[9]  Tsung-Cheng Chang,et al.  microRNAs in vertebrate physiology and human disease. , 2007, Annual review of genomics and human genetics.

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

[11]  Martin W. McBride,et al.  Gene expression profiling in whole blood of patients with coronary artery disease , 2010, Clinical science.

[12]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

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

[14]  David A Stenger,et al.  Assessment of two methods for handling blood in collection tubes with RNA stabilizing agent for surveillance of gene expression profiles with high density microarrays. , 2003, Journal of immunological methods.

[15]  C. Bauters,et al.  [Pathophysiology of coronary artery disease]. , 2008, La Revue du praticien.

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

[17]  Jason Laramie,et al.  Whole blood and leukocyte RNA isolation for gene expression analyses. , 2004, Physiological genomics.

[18]  Thomas D. Schmittgen,et al.  MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. , 2006, The Journal of Biological Chemistry.

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

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

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