Assessment of micro ribonucleic acids after exercise: Is this the future to detect coronary artery disease at its early stage?

Abstract

Coronary artery disease (CAD) is still the leading cause of death in males and females and based on the recent report from the American Heart Association it was calculated that each minute someone in the United States dies from a heart disease. Therefore, early detection of CAD is an important and demanding task for clinicians to initiate appropriate treatment and for risk prediction. Unfortunately the tools available are lacking sensitivity or are cost intensive and are only available in limited centres. While the use of blood biomarker such as high-sensitivity cardiac troponin is indispensable for early diagnosis of myocardial infarction, a specific and highly sensitive blood biomarker for CAD is still not available. After being considered as ‘junk’ in the human genome, non-coding ribonucleic acids (RNAs), such as micro RNAs (miRNAs) or long non-coding RNAs, currently represent one of the leading frontiers in cardiovascular science. In particular miRNAs emerged as potential therapeutic targets and may represent possible biomarkers for early detection of disease development. miRNAs are short ( 20–30 nucleotides), highly conserved functional non-coding regulatory molecules that play a key role in regulating gene expression (reviewed in Small and Olson). The identification of circulating miRNAs in blood and other body fluid has immediately gained the attention of clinical research for their potential utility as biomarkers. Besides serving as biomarker, a recent study in patients with an acute coronary syndrome clearly documented that miRNA level can even be regarded as a prognostic marker since a significant association with six month mortality was evident. Is something like this also available for the diagnosis of CAD and for predicting mortality? In recent years the use of miRNA as a biomarker in CAD was tested in several studies but unfortunately the pattern of miRNA regulation varies from study to study and the results are not comparable (summarized in Malik et al.). A major problem with miRNAs is that more than 1900 different human miRNAs have been discovered and each of these miRNAs regulates not just a single gene, and that each of these studies analysed different sets of miRNAs. Therefore, instead of quantifying a single miRNA, the analysis of miRNA patters may be more promising. Several studies using selected miRNAs, such as miR-499, miR-21, miR-208a, miR-144 and miR-33, were performed aiming to identify miRNAs that predict CAD. Whereas two studies concluded that the selected miRNAs were associated with the presence and severity of CAD, the study by Hortmann and colleagues concluded that the selected miRNAs did not provide additional clinical value regarding the detection of CAD. Therefore, at the moment no clear proven pattern of miRNAs is available to diagnose CAD, especially in its early stage. In the current issue of the European Journal of Preventive Cardiology Barbara Mayr and colleagues present a study in which they analysed 187 target miRNAs in 20 CAD and 20 non-CAD patients before and after a single bout of exercise (all-out exercise test on a cycle ergometer). Blood was drawn before and immediately after the exercise test and plasma was isolated by centrifugation for quantification of circulating miRNAs. At baseline the analysis of 18 miRNAs allowed discrimination between CAD and no-CAD. In response to exercise training 51 miRNAs were modulated in healthy controls, whereas this number was slightly higher in CAD patients. After doing a logistic regression analysis the authors concluded that four miRNAs, one measured at rest (miR-150-5p) and three in response to exercise (miR-101-3p, miR-141-3p and miR-200b-3p), together with maximal oxygen uptake and maximal power corrected for body