MicroRNAs expression profiles in cardiovascular diseases

Abstract

The current search for new markers of cardiovascular diseases (CVDs) is explained by the high morbidity and mortality still observed in developed and developing countries due to cardiovascular events. Recently, microRNAs (miRNAs or miRs) have emerged as potential new biomarkers and are small sequences of RNAs that regulate gene expression at posttranscriptional level by inhibiting translation or inducing degradation of the target mRNAs. Circulating miRNAs are involved in the regulation of signaling pathways associated to aging and can be used as novel diagnostic markers for acute and chronic diseases such as cardiovascular pathologies. This review summarizes the biogenesis, maturation, and stability of miRNAs and their use as potential biomarkers for coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF).

Figure 1

The miRNA or canonical pathway produces pri-miRNA transcripts from miRNA genes by RNA polymerase II or III (RNA pol II/III) followed by Drosha/DGCR8 processing of the pri-miRNA transcripts into pre-miRNAs. Intronic pre-miRNA hairpins of the mirtron or noncanonical pathway, transcribed by RNA polymerase II (RNA pol II), are formed by splicing (spliceosome), debranching, and trimming of short introns (lariat) without Drosha processing. Pre-miRNAs generated by both pathways are exported from the nucleus via exportin-5 (Exp 5), followed by subsequent Dicer/TRBP which generates double-stranded-RNAs called miRNA/miRNA*. Argonaute proteins (Ago) unwind and separate the guide strand (miRNA) and the passenger strand (miRNA*). The RISC (RNA-induced silencing complex) incorporates the mature miRNA and interacts with the 3′-UTR of the target mRNA and regulates gene expression by translation inhibition or mRNA degradation.

Figure 2

The most relevant miRNAs reported as promising biomarkers in coronary heart disease (a), myocardial infarction (b), and heart failure (c). ACS: acute coronary syndrome; AMI: acute myocardial infarction; CAD: coronary heart disease; DCM: dilated cardiomyopathy; Down: downregulated; EMB: endomyocardial biopsy; EOCs: early outgrowth cells; FGP: fetal gene program; h: hours; HF: heart failure ICM: ischemic cardiomyopathy; LV: left ventricle; LVB: left ventricle biopsies; MI: myocardial infarction; MPs: microparticles; NYHA: New York Heart Association; NSTEMI: non-ST elevation myocardial infarction; PBMCs: peripheral blood mononuclear cells; SAP: stable angina pectoris; SF: severe fibrosis; STEMI: ST elevation myocardial infarction; UA: unstable angina; UAP: unstable angina pectoris; UP: upregulated.