Differentially expressed mRNAs and their upstream miR-491-5p in patients with coronary atherosclerosis as well as the function of miR-491-5p in vascular smooth muscle cells.

MicroRNAs (miRNAs) regulate gene expression and are biomarkers for coronary atherosclerosis (AS). A novel miRNA-mRNA regulation network of coronary AS still needs to be disclosed. The aim of this study was to analyze potential mRNAs in coronary AS patients and the role of their upstream miR-491-5p in vascular smooth muscle cells (VSMCs). We first confirmed top ten mRNAs according to the analysis from Gene Expression Omnibus database (GSE132651) and examined the expression levels of them in the plaques and serum from AS patients. Five mRNAs (UBE2G2, SLC16A3, POLR2C, PNO1, and AMDHD2) presented significantly abnormal expression in both plaques and serum from AS patients, compared with that in the control groups. Subsequently, they were predicted to be targeted by 11 miRNAs by bioinformatics analysis. Among all the potential upstream miRNAs, only miR-491-5p was abnormally expressed in the plaques and serum from AS patients. Notably, miR-491-5p overexpression inhibited viability and migration, and significantly increased the expression of contractile markers (α-SMA, calponin, SM22α, and smoothelin) in VSMCs. While silencing miR-491-5p promoted viability and migration, and significantly suppressed the expression of α-SMA, calponin, SM22α, and smoothelin. Overall, miR-491-5p targeted UBE2G2, SLC16A3, and PNO1 and regulated the dysfunctions in VSMCs.

MicroRNA-219-5p participates in cyanotic congenital heart disease progression by regulating cardiomyocyte apoptosis.

MicroRNAs (miRs) play important roles in the protection against and development of congenital heart disease (CHD). However, the role and potential mechanisms of miR-219-5p in cyanotic CHD remains unclear. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure miR-219-5p levels in cyanotic CHD and hypoxia-induced H9C2 cells. Dual luciferase reporter gene assay was used to confirm whether liver receptor homolog-1 (LRH-1) was a direct target of miR-219-5p. miR-219-5p inhibitor and LRH-1-small interfering RNA were transfected into H9C2 cells under hypoxic conditions to investigate the role of miR-219-5p in hypoxia-induced H9C2 cells. Subsequently, cell viability was detected using an MTT assay and cell apoptosis was detected using flow cytometry. In addition, RT-qPCR and western blotting assays were performed to detect the mRNA and protein expression of LRH-1, cyclin D1 and ß-catenin, respectively. The data showed that miR-219-5p expression was higher in patients with cyanotic CHD compared with patients with acyanotic CHD gradually increased in H9C2 cells with prolonged hypoxia time. Dual luciferase reporter assay results showed that LRH-1 was a direct target gene of miR-219-5p. Inhibition of miR-219-5p reversed hypoxia-induced cell viability reduction and attenuated hypoxia-induced cell apoptosis. In addition, hypoxia induction inhibited the expression of LRH-1, cyclin D1 and ß-catenin, which was reversed by miR-219-5p inhibitor. However, LRH-1 downregulation reversed the miR-219-5p inhibitor enhanced cell viability, decreased cell apoptosis and increased expression of LRH-1, cyclin D1 and ß-catenin in hypoxia-treated cardiomyocytes. The present results demonstrated that downregulation of miR-219-5p promoted the expression of the LRH-1/Wnt/ß-catenin signaling pathway-associated components, reduced cardiomyocyte apoptosis and increased cell growth under hypoxic conditions. miR-219-5p may be a potential therapeutic target for cyanotic CHD therapy.

Circulating miR-106a may Function as Potential Biomarkers in Patients with Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) is a common cardiovascular disorder, and CAD is also the main cause of sudden cardiac death. Thus, identification of novel biomarkers for the early diagnosis and treatment of CAD is urgently needed. This study aims to explore the clinical significance of the plasma level of miR-106a in CAD. METHODS: A total of 92 patients were enrolled in the present study, and 92 healthy volunteers were enrolled as the control. The plasma samples of the participants were collected, and the expression levels of miR-106a in the plasma of the patients and healthy controls were compared by RT-qPCR methods. Moreover, the association between the plasma level of miR-106a and the SYNTAX scoring (SS) of the patients were analyzed. Finally, the serum levels of 25 (OH) D3 and oxidized low-density lipoprotein (ox-LDL) between the patients and healthy controls were compared, and the correlation between the plasma level of miR-106a and the serum level of 25 (OH) D3 and ox-LDL in patients with CAD were analyzed. RESULTS: miR-106a was significantly up-regulated in plasma of patients with CAD. Results of receiver operation characteristics (ROC) curve showed that the plasma level of miR-106a is a sensitive biomarker for the diagnosis of CAD (AUC = 0.8189, 95% CI = 0.7578 to 0.8799). Furthermore, the plasma level of miR-106a was positively correlated with the SS of the patients. Finally, ox-LDL was markedly increased and 25 (OH) D3 was significantly de-creased in the serum of patients with CAD. The plasma level of miR-106a was positively correlated with the level of ox-LDL and negatively correlated with the level of 25 (OH) D3 in patients with CAD. CONCLUSIONS: miR-106a was up-regulated in CAD, and miR-106a may serve as a potential biomarker for the early diagnosis and evaluation of clinical outcomes of CAD.

Ruptured Bronchial Artery Aneurysm Treated With Aortic Stent Graft and Aneurysm Embolization.

BACKGROUND: Mediastinal bronchial artery aneurysms are uncommon, with fewer than 40 published case reports. This study objective was to evaluate the short term follow up of two cases ruptured Bronchial Artery Aneurysm (rBAA) treated with aneurysm embolization and subsequent aortic stent graft. METHODS: Two cases of rBAA were treated with a combination of an aortic stent-graft and aneurysm embolization. With rBAA, aneurysm embolization could be performed with sodium polymannuronate until the aneurysm was almost completely packed. One of the limitations of aneurysm embolization is spontaneous recanalization of previously occluded aneurysm. So a stent-graft was deployed to isolate the feeding artery of the rBAA from the descending aorta. The 3 months follow- up after the procedure included chest or back pain and computed tomographic angiography. RESULTS: The hospital stays of the 2 cases were 5 and 7 days. Chest or back pain was disappeared. There were no hospital deaths and late deaths. Computed tomographic angiogram showed no recanalization and no hemothorax. These 2 patients have not reported any complications up to now. CONCLUSION: Aortic stent graft combined with aneurysm embolization is a minimally invasive, effective and safe method for rBAA.

miR-98 inhibits cell proliferation and induces cell apoptosis by targeting MAPK6 in HUVECs.

The aim of current study was to explore the role of microRNA (miR)-98 in atherosclerosis. Human vascular endothelial cells (HVECs) were isolated from the peripheral blood of healthy volunteers and patients with atherosclerosis. Compared with endothelial cells from the healthy control group, the expression level of mitogen activated protein kinase (MAPK)6 was significantly upregulated and miR-98 was downregulated in the endothelial cells of patients with atherosclerosis. The human umbilical vein endothelial cell line (HUVEC) was adopted to perform in vitro studies. Overexpression of miR-98 reduced the proliferation and induced the apoptosis of HUVECs, which were revealed using an MTT assay, and flow cytometry assay, respectively. The aforementioned influences of miR-98 on HUVECs were mediated by targeting MAPK6, which was verified using luciferase assays. Additionally, the overexpression of miR-98 reduced the protein level of apoptosis regulator Bcl-2 and MAPK6; however, it induced the protein expression of caspase-3 and apoptosis regulator Bax. In conclusion, these findings demonstrate that miR-98 is an important regulator of atherosclerosis, suggesting that miR-98 may be a potential therapeutic target for the treatment of atherosclerosis.

Premature senescence of cardiac fibroblasts and atrial fibrosis in patients with atrial fibrillation.

Premature senescence is associated with atrial fibrosis and has an antifibrotic effect in mice. However, the role of senescence in atrial fibrillation (AF) remains unclear. Here, we investigated the association of premature senescence with fibrosis and also determined the role of senescence in the recurrence of AF after surgery ablation. Western blot, Sirius red staining, SA-ß-gal staining and immunohistochemistry were performed to detect the degree of atrial fibrosis ,the expression of TGF-ß and collagens, and also the senescence markers in 72 tissue specimens of left atrial appendage in this study. Then the patients undergoing successful surgical ablation were followed up for 12 months. The expression of collagens and TGF-ß was paralleled by a high level of atrial fibrosis and were increased in AF group, especially in the persistent AF group. Western blotting of P16 and SA-ß-gal staining showed an increased premature senescence in the sinus rhythm, paroxysmal AF and persistent AF groups. In addition, positive area of senescence markers, SA-ß-gal and P16, was correlated positively with fibrotic lesions. We also found a lower ratio of P16/TGF-ß in patients with recurrence of AF than in patients without recurrent AF. In conclusion, premature senescence is associated with atrial fibrosis in AF, and may have an antifibrotic role in AF.

Comparison of clinical outcomes and postoperative recovery between two open heart surgeries: minimally invasive right subaxillary vertical thoracomy and traditional median sternotomy.

OBJECTIVE: To compare the clinical outcomes of minimally invasive right subaxillary vertical thoracotomy and traditional median sternotomy through right atrium in treatment of common congenital heart diseases. METHODS: Clinical data of 59 cases of common congenital heart diseases treated with minimally invasive right axillary vertical thoracotomy from May, 2011 to February, 2013 and 77 cases of same diseases with traditional median sternotomy in the past three years were retrospectively analyzed, including atrial septal defect, membranous ventricular septal defect and partial endocardial cushion defect. The results were compared from the two groups, including the time for operation and cardiopulmonary bypass, amount of blood transfusion, postoperative drainage, ventilation time, hospital stay, and prognosis. RESULTS: No severe complications happened in both groups, like deaths or secondary surgery caused by bleeding. No significant differences were in CPB time and postoperative ventilator time between groups (P>0.05), while for all of the operative time, the length of incision, postoperative drainage and hospital stay, minimally invasive right axillary vertical thoracotomy was superior to median sternotomy, with statistically significant differences (P<0.05). In six-month followup after operation, no complications of residual deformity and pericardial effusion were found in both groups by doing echocardiography, but mild pectus carinatum was found in 8 patients in the traditional median sternotomy group (traditional group), whereas patients in another group were well recovered. CONCLUSIONS: Minimally invasive right subaxillary vertical thoracotomy for common congenital heart diseases is as safe as traditional median sternotomy, without the increasing incidence of postoperative complications. Additionally, compared with traditional median sternotomy, minimally invasive right subaxillary vertical thoracotomy is better in the aspects of hidden incision, appearance, and postoperative recovery.

Hybrid treatment of a dislocated atrial septal occluder device at the bifurcation of the left and right common iliac artery.

Percutaneous closure of secundum atrial septal defects (ASDs) with atrial septal occluders (ASOs) avoids sternotomy and cardiopulmonary bypass, and thus is commonly preferred to open heart surgery. However, rare reports of dislocation of the ASO into the systemic circulation do exist. We report the use of an emergent hybrid procedure in the dislocation of an ASO at the bifurcation of the left and right common iliac artery. The dislocation was diagnosed 7 days after percutaneous closure of an ASD.

Combination of aortic stent-graft and arterial embolization for ruptured bronchial artery aneurysm.

Bronchial artery aneurysm is a rare condition. Rupture of bronchial artery aneurysm can cause a critical hemorrhage. We report a case of ruptured bronchial artery aneurysm mimicking a clinical picture of aortic dissection with right hemothorax. The patient was treated with a combination of an aortic stent-graft and arterial embolization. Recovery was uneventful and the patient's follow-up result in 1 year was well. Combination treatment is feasible and accurate for ruptured bronchial artery aneurysm. The present study is among the few in which an aortic stent-graft has been used for a bronchial artery aneurysm.