miR-141-5p suppresses vascular smooth muscle cell inflammation, proliferation, and migration via inhibiting the HMGB1/NF-κB pathway.

MicroRNAs (miRNAs) have been identified as significant modulators in the pathogenesis of atherosclerosis (AS). Additionally, the dysregulation of vascular smooth muscle cells (VSMCs) is a crucial biological event during AS. Our study aimed to explore the functional roles and molecular mechanisms of miR-141-5p in VSMCs dysfunction. C57BL/6 mice were used to establish AS animal model. Human VSMCs were treated by oxidized low-density lipoprotein (ox-LDL) to establish AS cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to probe miR-141-5p and high-mobility group box 1 (HMGB1) mRNA expressions in VSMCs or plasma samples of the mice. Inflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. Cell counting kit-8 and bromodeoxyuridine assays were performed to evaluate cell proliferation. Cell migration and apoptosis were detected with Transwell assay and flow cytometry analysis, respectively. The target gene of miR-141-5p was predicted with the TargetScan database, and the interaction between miR-141-5p and HMGB1/nuclear factor-κB (NF-κB) was further validated by dual-luciferase reporter assay, qRT-PCR, and Western blot analysis. miR-141-5p was found to be decreased in the plasma of patients and mice model with AS. Its expression was also downregulated in VSMCs treated by ox-LDL. miR-141-5p overexpression inhibited the inflammation, proliferation, migration of VSMCs, and promoted the apoptosis of VSMCs. HMGB1 was identified as a direct target of miR-141-5p, and miR-141-5p could repress the activity of HMGB1/NF-κB signaling. HMGB1 restoration reversed the effects of miR-141-5p, and NF-κB inhibitor JSH-23 showed similar effects with miR-141-5p mimics. miR-141-5p inhibits VSMCs' dysfunction by targeting the HMGB1/NF-κB pathway, which probably functions as a protective factor during the development of AS.

MicroRNA-140 attenuates myocardial ischemia-reperfusion injury through suppressing mitochondria-mediated apoptosis by targeting YES1.

Myocardial ischemia-reperfusion (I/R) injury is thought to have its detrimental role in coronary heart disease (CHD), which is considered as the foremost cause of death all over the world. However, molecular mechanism in the progression of myocardial I/R injury is still unclear. The goal of this study was to investigate the expression and function of microRNA-140 (miR-140) in the process of myocardial I/R injury. The miR-140 expression level was analyzed in the myocardium with I/R injury and control myocardium using quantitative real-time polymerase chain reaction. Then the relation between the level of miR-140 and YES proto-oncogene 1 (YES1) was also investigated via luciferase reporter assay. Assessment of myocardial infarct size measurement of serum myocardial enzymes and electron microscopy analysis were used for analyzing the effect of miR-140 on myocardial I/R injury. We also used Western blot analysis to examine the expression levels of the mitochondrial fission-related proteins, Drp1 and Fis1. miR-140 is downregulated, and YES1 is upregulated after myocardial I/R injury. Overexpression of miR-140 could reduce the increase related to myocardial I/R injury in infarct size and myocardial enzymes, and it also could inhibit the expression of proteins related to mitochondrial morphology and myocardial I/R-induced mitochondrial apoptosis by targeting YES1. Taken together, these findings may provide a novel insight into the molecular mechanism of miR-140 and YES1 in the progression of myocardial I/R injury. MiR-140 might become a promising therapeutic target for treating myocardial I/R injury.

Mitochondrial genome mutations in 13 subunits of respiratory chain complexes in Chinese Han and Mongolian hypertensive individuals.

Mitochondrial DNA (mtDNA) mutations are associated with cardiovascular disease, including hypertension (HTN). Here we performed a genetic and molecular analysis of 13 mtDNA-encoded subunits of respiratory chain complexes in 100 Chinese Han and 80 Mongolian HTN cases, and 100 Han and 42 Mongolian normotension subjects. The total cholesterol of the Mongolian normotensive subjects was higher than that of the Han normotensive group (p < .05). Sequence analysis identified 636 point mutations in the 13 mtDNA-encoded subunits in the Han and Mongolian hypertensive individuals, including 66 in NADH dehydrogenase subunit 1(ND1), 62 in ND2, 71 in COI, 29 in COII, 17 in ATP8, one in ATP6/8, 49 in ATP6, 27 in COIII, 27 in ND3, 14 in ND4L, 74 in ND4, 97 in ND5, 24 in ND6, and 78 in CYTB. Eight of these point mutations were present at significantly different frequencies in Han and Mongolian hypertensive individuals. Thirty-one point mutations were present only in Mongolian hypertensive individuals, while 73 were present only in Han hypertensive individuals. The relation between point mutations in 13 mtDNA-encoded subunits of respiratory chain complexes and HTN is worth to further research in future; however, the functional effects of these mutations require elucidation.

Feasibility and safety of transthoracic echocardiography-guided transcatheter closure of atrial septal defects with deficient superior-anterior rims.

Although previous studies showed that transthoracic echocardiography (TTE) can be used to guide transcatheter closure of atrial septal defect (ASD), whether TTE can be used to guide transcatheter closure of secundum ASD with a deficient superior-anterior rim is unknown and this critical issue was addressed in the present study. A total of 280 patients with secundum ASD who underwent transcatheter ASD closure were recruited and divided into groups A and B depending on ASD superior-anterior rim>4 mm (n = 118) or ≤4 mm (n = 162). TTE was used to guide Amplatzer-type septal occluder (ASO) positioning and assess residual shunt. Procedure success was defined as no, trivial and small residual shunt immediately after the procedure as assessed by color Doppler flow imaging. Group A and group B did not differ in complication rate (8.55% vs.7.55%), procedure success rate (98.3% vs. 95.0%) or complete closure rate immediately after the procedure (89.7% vs. 89.3%) or at 6-month follow-up (98.3% vs. 96.8%). The mean procedure and fluoroscopy time in group B were much longer than those in group A. In conclusion, the absence of a sufficient superior-anterior rim in patients undergoing percutaneous closure of secundum-type ASDs using fluoroscopic and TTE guidance is associated with slightly greater device malposition and migration as well as increased procedural and fluoroscopic times, but the overall complication rate did not differ with TTE guidance when compared to historical controls that used TEE guidance.