ABSTRACT
BACKGROUND: Myocardial infarction is one of the most common causes of death, and the number of individuals at risk is increasing. A rapid and accurate differential diagnosis of myocardial infarction is crucial for timely interventions and for improvement of the prognosis. However, it is difficult to achieve using current methods. To better manage this condition, improved tools for risk prediction, including more accurate biomarkers, are needed. METHODS: We studied the expression of microRNA-539 (miR-539) and of MEK protein using a rat model of myocardial infarction. RESULTS: The results of our experiments demonstrated an increase in the expression of miR-539 and a decrease in the expression of MEK. Furthermore, we observed that miR-539 inhibited the expression of MEK through targeting of the 3'UTR of MEK; this led not only to suppressed proliferation but also to apoptosis and autophagy of H9C2 cells. CONCLUSION: Overexpression of miR-539 plays a role in the degree of myocardial infarction. On the basis of our results, we conclude that miR-539 may be a potential therapeutic target for myocardial infarction.
Subject(s)
Disease Models, Animal , Genetic Predisposition to Disease/genetics , MAP Kinase Signaling System/genetics , MicroRNAs/genetics , Myocardial Infarction/genetics , 3' Untranslated Regions/genetics , Animals , Apoptosis/genetics , Autophagy/genetics , Cell Death/genetics , Cell Line , Cell Proliferation/genetics , Gene Expression Regulation/genetics , Humans , Rats, Sprague-Dawley , Risk AssessmentABSTRACT
OBJECTIVE: The aim of the study was to investigate whether functional changes and structural remodeling occurs in the microvascular bed of the pulmonary circulation under nonpulsatile flow perfusion. MATERIALS AND METHODS: An animal model of unilateral nonpulsatile flow in the right lung was established in dogs. Streptavidin-biotin enzyme complex (SP method) was used to detect the expression of endothelial nitric oxide synthase (eNOS) in vascular endothelial cells and the apoptosis-related protein Fas in smooth muscle cells of the pulmonary artery of both lungs, and structural changes of the arterioles in the capillary bed of both lungs were observed under light microscope. RESULTS: eNOS expression in right lung arterioles with nonpulsatile flow perfusion was significantly lower than in the left lung (10,846.7 ± 177.8 vs. 13,136.1 ± 189.6; T = 2.24, P < 0.05). Expression of the apoptosis-related protein Fas in smooth muscle cells of the arteriole of the right lung was significantly higher than in the left lung (14,254.1 ± 217.1 vs. 11,976.7 ± 195.7; T = 2.16, P < 0.05). Image analysis of pulmonary arterioles showed that the ratio of vascular wall thickness and the external vessel diameter (13.64% ± 12.8% vs. 14.96% ± 13.1%) and the ratio of vascular wall area and the total vessel area (46.4% ± 11.7% vs. 47.8% ± 12.2%) of the right lung were significantly lower than in the left lung. CONCLUSIONS: Long-term nonpulsatile flow perfusion of the Fontan circulation can decrease the synthesis of eNOS in endothelial cells of the pulmonary vessels, increase the apoptosis of smooth muscle cells of the arteriole wall, and lead to arterial venous conversion and pulmonary vessel remodeling.
