The role of miR-19b in the inhibition of endothelial cell apoptosis and its relationship with coronary artery disease

Inflammatory factors can destroy the integrity of the endothelium, triggering the development of atherosclerosis. Tumor necrosis factor-α (TNF-α), an important inflammatory factor, induces endothelial cell injury, which results in endothelial dysfunction1,2. The caspase family members, including initiator caspases (e.g., caspase-8, -9, and -10) and effector caspases (e.g., caspase-3 and -7), are essential to the apoptotic process3. Numerous risk factors related to coronary artery diseases (CAD) contribute to increases in circulating TNF-α concentrations, resulting in higher caspase expression3. Therefore, reducing caspase levels may be helpful in attenuating both the development and the progression of CAD. MicroRNAs (miRNAs), which consist of 18 to 24 nucleotides, can negatively regulate gene expression by binding to sites in the 3′ untranslated region (3′-UTR) of a target mRNA. Approximately 1000 miRNAs have been identified in humans4. Each miRNA can regulate hundreds of target mRNAs, as well as nearly one-third of proteins4,5. As a result, the biological effects of miRNAs are extensive and include cell growth, differentiation, and apoptosis. In recent years, circulating miRNAs have been widely recognized as biomarkers of coronary heart disease6,7. Researchers have noted that the miR-17-92 cluster is significantly downregulated among patients with atherosclerosis8. The miR-17-92 cluster, which includes miR-17, miR-18a, miR-19a/b, miR-20a and miR-92a, has been extensively studied in different types of cancers9,10 (Table 1). Research has also demonstrated that miR-19 and miR-92 act to maintain an intricate balance between the pathways that promote and suppress cancer11. miR-17 and miR-20a influence cellular proliferation via the E2F family of transcription factors12. Additionally, miR-17-92 is highly expressed in normal human endothelial cells13. Researchers have noted that inhibiting miR-92a results in enhanced blood vessel growth and the functional recovery of damaged tissues13. miR-17/20 exhibits cell-intrinsic anti-angiogenic activity in endothelial cells14. These findings suggest that a specific miR-17-92 family member may be involved in the development of cardiovascular disease. However, whether the miR-17-92 cluster regulates apoptotic gene expression in endothelial cells needs to be further studied. Table 1 Overview of the miR-17–92 cluster. PTEN (a phosphatase and tensin homolog deleted from chromosome 10) is regulated by TNF-α and plays a crucial role in apoptosis15,16. Additionally, PTEN is a target gene of miR-17-9217, which suggestes that PTEN contributes to TNF-α induced apoptosis in endothelial cells. However, it remains unclear whether the miR-17-92 cluster is associated with endothelial dysfunction; therefore, the aim of this study was to analyze the changes in the levels of the miR-17-92 cluster in clinical patient sample and determine the role that the miR-17-92 cluster may play in various signaling pathways associated with TNF-α-induced endothelial cell apoptosis.