Coronary artery disease (CAD), including acute myocardial infarction (AMI) is the complication of atherosclerosis. Recently, genome-wide association studies have identified a large number of CAD-related genetic variants. However, only 10% of CAD cases could be explained. Low frequent and rare genetic variants have been recently proposed to be main causes for CAD. SIRT2 is a member of sirtuin family, NAD(+)-dependent class III deacetylases. SIRT2 is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy, as well as in platelet function. Thus, we hypothesized that genetic variants in SIRT2 gene may contribute to AMI. In this study, SIRT2 gene promoter was analyzed in large cohorts of AMI patients (n = 375) and ethnic-matched controls (n = 377). Three novel heterozygous DSVs (g.38900888_91delTAAA, g.38900270A>G and g.38899853C>T) were identified in three AMI patients, but in none of controls. These DSVs significantly altered the transcriptional activity of the SIRT2 gene promoter (P<0.05) in both HEK-293 and H9c2 cells. Five novel heterozygous DSVS (g.38900562C>T, g.38900413A>C, g.38900030G>A, g.38899925A>C and g.38899852C>T) were only found in controls, which did not significantly affected SIRT2 gene promoter activity (P>0.05). In addition, four novel heterozygous DSVs and five SNPs were found in both AMI patients and control with similar frequencies (P>0.05), two SNPs of which were examined and did not affect SIRT2 gene promoter activity (P>0.05). Taken together, the DSVs identified in AMI patients may change SIRT2 level by affecting the transcriptional activity of SIRT2 gene promoter, contributing to the AMI development as a rare risk factor.

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LC3 gene expression in the peripheral leucocytes was significantly decreased in patients with CAD, indicating that autophagosome formation is decreased. These data suggest that autophagy in circulating leucocytes may be involved in the pathogenesis of atherosclerosis and CAD.

MicroRNA (miR)-128-3p is a brain-enriched miRNA that participates in the regulation of neural cell differentiation and the protection of neurons, but the mechanisms by which miR-128-3p regulates its target and downstream genes to influence cell fate from adult stem cells are poorly understood. In this study, we show down-regulation of miR-128-3p during all-trans retinoic acid (ATRA)-induced neurogenic differentiation from amniotic epithelial cells (AECs). We investigated miR-128-3p in both the Notch pathway and in the expression of neuron-specific genes predicted to be involved in miR-128-3p signaling to elucidate its role in the genetic regulation of downstream neurogenic differentiation. Our results demonstrate that miR-128-3p is a negative regulator for the transcription of the neuron-specific genes β III-tubulin, neuron-specific enolase (NSE), and polysialic acid-neural cell adhesion molecule (PSA-NCAM) via targeting Jagged 1 to inhibit activation of the Notch signaling pathway. We also used bioinformatics algorithms to screen for miR-128-3p interactions with long non-coding (lnc) RNA and circular RNA as competing endogenous RNAs to further elucidate underlying downregulated molecular mechanisms. The lncRNA maternally expressed 3 is up-regulated by the ATRA/cAMP/CREB pathway, and it, in turn, is directly down-regulated by miR-128-3p to increase the amount of neuron differentiation. Endogenous miRNAs are, therefore, involved in neurogenic differentiation from AECs and should be considered during the development of effective cell transplant therapies for the treatment of neurodegenerative disease.