MiRNA Expression Profile of the Myocardial Tissue of Pigs with Coronary Microembolization

Abstract

Background/Aims: Coronary microembolization (CME) is a serious complication of coronary heart disease and is considered as a strong predictor of poor long-term prognosis and major cardiac adverse events. Here, we identified differentially expressed microRNAs (miRNAs) in the myocardial tissue of CME pigs, and predicted and analyzed the possible functions of their target genes. Methods: Twelve Bama mini-pigs were randomly assigned to the sham and CME group (n = 6 in each group). The two groups were compared with regard to heart function, area of infarction, cardiomyocyte apoptosis, and myocardial expression of TNF-α, IL-1β and IL-6. Further, miRNA chip analysis was used to screen for differentially expressed miRNAs, and the results were validated by real-time PCR. Bioinformatics methods were used to predict and analyze the functions of the target genes of the identified miRNAs. Results: The model CME pigs showed significantly increased expression of TNF-α, IL-1β and IL-6, as well as micro-infarction lesions and cell apoptosis in the myocardial tissue. Thus, the model was established successfully. In the myocardial tissue of the CME pigs, the expression of ssc-miR-92b-5p, ssc-miR-491, ssc-miR-874, ssc-miR-425-3p, ssc-miR-376a-5p, ssc-miR-370, ssc-miR-30c-3p, ssc-miR-493-5p and ssc-miR-323 was significantly increased, whereas the expression of ssc-miR-136 and ssc-miR-142-3p was significantly decreased. GO and KEGG pathway analysis indicated that the target genes of these miRNAs are mainly associated with cell proliferation, apoptosis, necrosis, inflammation, and fibrosis. Conclusion: The differentially expressed miRNAs identified in the myocardial tissue of CME pigs could be new biomarkers or potential treatment targets for CME.

Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury

“…Currently, it is believed that the inflammatory response in the myocardium might be the main cause of progressive systolic dysfunction [3,19]. Our previous animal experiments demonstrated that large amounts of inflammatory cells infiltrate micro-infracted lesions in the myocardium after CME, accompanied with a massive release of inflammatory factors, leading to local inflammatory response in the myocardium; this could be considered the central cause of myocardial injury and progressive cardiac dysfunction after CME [20,21]. Further experiments found that inflammatory factors in myocardial tissues, e.g.…”

Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway

“…Very little research has focused on the expression of miR-136-3p in human or experimental CAD. A previous study on atherosclerosis has indicated that miR-136 was abnormally expressed in vascular smooth muscle cells, and its alteration mediates atherosclerosis through the influence on cell proliferation [14], and ssc-miR-136 has been reported to be broadly decreased in the myocardial tissue of pigs with coronary microembolization [33]. In this current study, we revealed that upregulation of miR-136-3p diminished the cardiomyocyte apoptosis in CAD rat models, as evidenced by lowered cleaved-caspase-3 and Bax as well as increased expression of Bcl-2.…”

A Hearty Dose of Noncoding RNAs: The Imprinted DLK1-DIO3 Locus in Cardiac Development and Disease

“…Gtl2/Meg3 lncRNA is downregulated in pulmonary smooth muscle cells subjected to hypoxia [ 100 ]. Consistent with these findings, lung tissue and pulmonary arteries from patients with pulmonary arterial hypertension (PAH) displayed reduced Gtl2/Meg3 expression [ 80 ]. Inhibition of Gtl2/Meg3 has been shown to promote proliferation of human pulmonary artery smooth muscle cells via the PTEN and p53 pathways, respectively [ 100 , 101 ].…”

“…In this same study, overexpression of miR-433 promoted cardiac fibroblast proliferation, and promoted pathological differentiation of fibroblasts into myofibroblasts [ 79 ]. Finally, miR-370 and miR-323 were upregulated in myocardial tissue from pigs subjected to coronary microembolization [ 80 ]. miR-370 was also expressed at significantly high levels in plasma from patients with coronary artery disease [ 81 ].…”