Until recently, miRNAs, which are cytoplasmic components, have been quantified in healthy/pathological tissues, a procedure that usually involves a surgical act. A recent clinical breakthrough occurred when miRNAs were detected in circulating body fluids together with other types of noncoding RNAs, DNAs, and mRNAs.80,81 They are detected in serum and EDTA-treated plasma, are very stable, can stand repetitive freeze-thaw cycles and are protected from RNases. 23 Moreover, a growing number of studies have shown that the levels of these circulating miRNAs vary significantly in pathological conditions such as various cancers, 82 myocardial infarction83,84 diabetes, 85 and so forth. An interesting article by Gupta et al86 provides the current knowledge about circulating miRNAs during CAD, myocardial infarction, and heart failure. Recently, Fichtlscherer et al23 performed miRNA profiles using RNA isolated from the blood of healthy volunteers and patients with stable CAD. They found that the expression of several miRNAs was significantly altered in patients. In the same study, they validated their results by quantitative PCR in 2 independent cohorts of patients and showed that the expression of miR-145, among other miRNAs, was significantly reduced in patients with CAD compared with healthy control patients. Thus, quantifying total blood levels of miR 143/145 and other experimentally validated miRNA candidates may provide a specific signature that could be an independent predictor of diagnosis, prognosis and/or etiology of CADs, keeping in mind that this concept will need comprehensive investigations to validate the theory. As a consequence, apart from being considered as potential therapeutic targets and the feasibility of these strategies become routinely available, we believe that the relationship between circulating miR-143/145 levels and CAD may at present serve as novel markers for diagnosis and prognosis of CAD and other vascular diseases. © 2011 American Heart Association, Inc.