Sheng-hua Zhou

Mesenchymal stem cells modified with miR-126 release angiogenic factors and activate Notch ligand Delta-like-4, enhancing ischemic angiogenesis and cell survival

The endothelial cell-specific microRNA (miRNA), miR-126, is considered a master regulator of physiological angiogenesis. Transplanted mesenchymal stem cells (MSCs) release soluble factors contributing to neoangiogenesis and cardiac repair. Therefore, we hypothesized that the over-expression of miR-126 may prolong MSC survival and enhance the cell secretome, thereby improving post-infarction angiogenesis and cardiac function. In this study, MSCs harvested from male C57BL/6 mouse bone marrow were infected in vitro with miR-126 (MSC(miR-126)) by using recombinant lentiviral vectors; the control cells were either non-transfected or transduced with mock vectors (MSC(null)). The results showed an increased secretion of angiogenic factors and a higher resistance against hypoxia in MSC(miR-126) compared with the control cells. The expression of the Notch ligand Delta-like (Dll)-4 in the MSC(miR-126) group was also increased. For in vivo experiments, MSC(miR-126) cultures were intramyocardially injected into the infarct region of the hearts of female C57BL/6 mice (an acute myocardial infarction model) who had undergone ligation of the left anterior descending coronary artery. The survival of MSC(miR-126) cultures, determined by Sry expression, was increased at 7 days after transplantation. MSC(miR-126)-treated animals showed significantly improved cardiac function as assessed by echocardiography 2 weeks later. The expression levels of angiogenic factors and Dll-4 in the infarcted myocardium were further increased by MSC(miR-126) compared with MSCs or MSC(null) cultures. Furthermore, fluorescent microsphere and histological studies revealed that myocardial blood flow and microvessel density were significantly increased in the MSC(miR-126)-transplanted animals. In addition, we found increased immature vessel proliferation following the transplantation of MSC(miR-126) cultures in which the expression of Dll-4 had been knocked down. However, blood vessels with lumen were barely detected, which indicated that Dll-4 plays a key role in tubulogenesis. We conclude that the transplantation of MSCs overexpressing miR-126 can further enhance functional angiogenesis in the ischemic myocardium possibly by the secretion of angiogenic factors and the activation of Dll-4, thus increasing MSC survival. Therefore, MSCs modified with miR-126 may represent a novel and efficient therapeutic approach for ischemic angiogenesis and the improvement of cardiac function.

Effect of Delayed vs Immediate Stent Implantation on Myocardial Perfusion and Cardiac Function in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention With Thrombus Aspiration

BACKGROUNDnOptimizing microcirculation in STEMI patients with thrombus-containing lesion undergoing percutaneous coronary intervention (PCI) remains challenging. Our objective was to compare the effects on myocardial perfusion and cardiac function of delayed vs immediate stent implantation after thrombus aspiration in STEMI patients undergoing PCI.nnnMETHODSnEighty-seven STEMI patients with thrombus-containing lesion undergoing PCI were enrolled. After thrombus aspiration was performed, subjects were divided into 2 groups according to residual thrombus score (TS): immediate stent implantation (ISI) group (n = 47, residual TS < 2; stenting was performed immediately), and delayed stent implantation (DSI) group (n = 40, residual TS ≥ 2; stenting was performed 7 days later). Corrected thrombolysis in myocardial infarction frame count and myocardial blush grade were analyzed immediately after PCI. The wall motion score index was assessed on admission and at 6-month follow-up.nnnRESULTSnAt the end of the PCI procedure, the corrected thrombolysis in myocardial infarction frame count was significantly shorter and the myocardial blush grade 3 was more frequent in the DSI group than in the ISI group. Compared with the ISI group, the DSI group had a lower incidence of thrombus-related angiographic events, including distal embolization and no reflow. A significantly greater improvement in wall motion score index from baseline to 6-month follow-up was observed in the DSI group compared with the ISI group.nnnCONCLUSIONSnIn STEMI patients presenting with thrombus containing lesion undergoing PCI, delayed stent implantation after thrombus aspiration leads to better myocardial perfusion and cardiac functional recovery in comparison with immediate stent implantation.

Complications associated with transcatheter closure of perimembranous ventricular septal defects

Objectives: To identify the complications associated with transcatheter closure of perimembranous ventricular septal defects (PmVSD) using the Amplazter PmVSD occluder (AGA Medical, USA). Methods: Between October 2002 and November 2006, transcatheter closure PmVSD was attempted in 210 patients and performed in 206 patients. Those patients were followed‐up for 6–24 months (mean, 10.6 ± 3.9 months) to identify the complications. Results: Device implantation was successfully accomplished in 206 of the 210 patients (98%). Serious complications such as high degree atrioventricular block (AV block), infective endocarditis, and device embolization occurred in eight cases (3.8%). Other complications including mild aortic or tricuspid regurgitation, femoral pseudoaneurysm, and femoral arteriovenous fistula occurred in four cases. Conclusions: Transcathter closure of PmVSD can be performed safely and successfully. But further studies should continue to evaluate the potential complications associated with this procedure.

Atrioventricular block: a serious complication in and after transcatheter closure of perimembranous ventricular septal defects.

Transcatheter closure is an effective approach for perimembranous ventricular septal defects (PMVSD). However, atrioventricular blocks (AVB) emerged possibly due to the close proximity of the PMVSD to the conduction system, but concern for the complication was not adequately emphasized. In this study, we report the incidence of AVBs, in and after transcatheter closure of a PMVSD, and the outcome of the complication in our center.

The effects and mechanisms of high loading dose rosuvastatin therapy before percutaneous coronary intervention in patients with acute coronary syndrome

atrial fibrillation: the Framingham study. N Engl J Med 1982;306(17):1018–22. [7] Movahed MR, Hashemzadeh M, Jamal MM. Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol 2005;105(3):315–8. [8] Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol 2002;40(3):418–23. [9] Kourliouros A, Karastergiou K, Nowell J, et al. Protective effect of epicardial adiponectin on atrial fibrillation following cardiac surgery. Eur J Cardiothorac Surg Feb 2011;39(2):228–32. [10] Lin YK, Chen YC, Chang SL, et al. Heart failure epicardial fat increases atrial arrhythmogenesis. Int J Cardiol May 25 2012, doi:10.1016/j.ijcard.2012.05.009.

Estrogen Treatment Inhibits Vascular Endothelial Senescence and Asymmetrical Dimethylarginine in Ovariectomized Rabbits

To investigate the effects of estrogen treatment on aortic endothelial senescence and atherosclerosis, an ovariectomized female rabbit model was constructed, and human umbilical vein endothelial cells were utilized to explore the potential mechanisms. Twenty-eight female rabbits were randomized into 4 groups (7 each): sham operation, ovariectomized, ovariectomized plus low-dose estradiol treatment, and ovariectomized plus high-dose estradiol treatment. All rabbits were fed on high-cholesterol diet for 12 weeks. Blood samples were collected to determine the serum estradiol, asymmetric dimethyl l-arginine (ADMA), and lipid levels, and the aortas were separated for histopathologic analysis. After ovariectomy and high-fat diet, the concentration of serum estradiols declined significantly (P < 0.01) and the levels of ADMA and serum lipids increased (all P < 0.01) as the area of senescent endothelium and atherosclerotic lesions enlarged (both P < 0.01). However, administration of estradiols reduced the levels of ADMA, total cholesterol, and low-density lipoprotein (LDL) cholesterol and inhibited endothelial senescence and atherosclerosis (all P < 0.01). Simultaneously, the concentration of high-density lipoprotein cholesterol and triglyceride increased (all P < 0.01). In vitro experiments also confirmed that estradiols could decrease the ADMA levels induced by oxidized LDL and inhibited oxidized LDL-induced and ADMA-induced human umbilical vein endothelial cell senescence. These results indicate that estrogens can inhibit endothelial senescence and atherosclerosis with reduced ADMA levels and improved lipid profile.

Retracted: The Effect of Early and Intensive Statin Therapy on Ventricular Premature Beat or Nonsustained Ventricular Tachycardia in Patients With Acute Coronary Syndrome

Retraction

The association between oxidative stress, activator protein-1, inflammatory, total antioxidant status and artery stiffness and the efficacy of olmesartan in elderly patients with mild-to-moderate essential hypertension

ABSTRACT This study investigated the change of oxidative stress, activator protein-1 (AP-1), inflammatory, total antioxidant status (TAS) and artery stiffness, and explored the relationship between these characteristics and the efficacy of olmesartan intervention in elderly patients with mild-to-moderate essential hypertension (EH). In total, 386 elderly patients with EH and 353 normotensive controls were recruited. All study subjects had oxidative stress markers, AP-1, inflammatory factors, TAS and brancial-ankle artery pulse wave velocity (ba-PWV) measured. In total, 193 elderly patients with EH were randomized to olmesartan and were matched with 193 normotensive controls to observe the change of index above mentioned before and after the treatment. Compared with the controls, superoxide dismutase (SOD) and TAS were significantly reduced in patients with EH, and malondialdehyde (MDA), AP-1, high-sensitivity C-reactive protein (Hs-CRP), Monocyte Chemoattractant Protein-1 (MCP-1), heart rate， endothelin-1 (ET-1), TAS and ba-PWV were significantly increased (P < 0.01 for all). Pearson’s correlation analysis showed that SOD and TAS were negatively related to AP-1 (P < 0.05 for all), and that blood pressure (BP), age, MDA, Hs-CRP, MCP-1, ET-1 were positively related to AP-1 (P < 0.01 for all). Multivariate linear regression analysis showed that BP, SOD, MDA, AP-1, Hs-CRP, MCP-1, ET-1, TAS, heart rate and age were independent risk factors for ba-PWV. After treatment with olmesartan, SOD and TAS were increased, while BP, heart rate, AP-1 and inflammatory factors were reduced with significant improvement in ba-PWV (P < 0.05 for all). More increase of arterial stiffness was reported in elderly hypertensive patients with greater oxidative stress, inflammatory, AP-1, heart rate, and lower TAS. Higher oxidative stress, AP-1 and inflammatory may predict higher arterial stiffness. Olmesartan may increase TAS, yet inhibit oxidative stress, AP-1, inflammatory, and heart rate with improved artery stiffness in elderly hypertensive patients.

Defibrillation threshold testing: Is it necessary during implantable cardioverter-defibrillator implantation?

Defibrillation threshold (DFT) testing has traditionally been a routine part of implantable cardioverter-defibrillator (ICD) implantation. DFT testing was developed in the early days of the ICD when failure of defibrillation was common, recipients had a high-risk of ventricular tachycardia (VT) or ventricular fibrillation (VF), and the only therapy for rapid VT or VF was a shock. However, modern ICD systems have such a high rate of successful defibrillation that many electrophysiologists now question whether DFT testing is still worthwhile. Studies found that long-term mortality was not higher among patients not undergoing DFT testing. Moreover, there was no survival difference between patients with a lower DFT and a higher DFT. Other studies have demonstrated that DFT testing poses some risk to the patient such as myocardial damage, embolic stroke in patient with atrial fibrillation and DFT testing-related death. If DFT testing is abandoned, more patients may have the opportunity to be treated with ICD, especially in regions with few or no electrophysiologists. It may be argued that other physicians, such as those currently implanting pacemakers, would more readily implant ICDs if not for the requirement of DFT testing.

Remnant-like lipoproteins may accelerate endothelial progenitor cells senescence through inhibiting telomerase activity via the reactive oxygen species-dependent pathway.

BACKGROUNDnWe previously found that remnant-like lipoproteins (RLPs), lipolytic products of triglyceride-rich lipoproteins including very low-density lipoprotein and chylomicron, can accelerate endothelial progenitor cell (EPC) senescence, which involves telomerase activity. The aim of this study was to investigate the effects of RLPs on telomerase activity and the catalytic subunit telomerase reverse transcriptase (TERT) in EPCs and the associated signal pathway.nnnMETHODSnRLPs were prepared from plasma samples by the immunoaffinity method. EPCs at day 8 were incubated with RLPs at 10-, 50-, 100-, and 200-μg/mL for 24 hours. Telomerase activity was measured with telomeric repeat amplification protocol assay, and optimum concentration of RLPs was determined. Human TERT (hTERT) and phosphorylated Akt protein kinase were detected by Western blot analysis in RLP-incubated EPCs with or without pretreatment of either superoxide dismutase or atorvastatin for 3 hours. Phosphorylated hTERT was measured by immunoprecipitation and Western blot assay. Nitrotyrosine was evaluated by immunofluorescence assay, and senescent EPCs were determined by senescence-associated β-galactosidase staining.nnnRESULTSnDose dependently, RLPs resulted in a decrease in telomerase activity, with a maximal effect at 200 μg protein/mL. The optimum concentration of RLPs was determined as 100 μg protein/mL. This dosage resulted in significant increases in senescence-associated β-galactosidase-positive cell and nitrotyrosine staining. In addition, RLPs decreased the expression of hTERT and repressed the phosphorylation of Akt and hTERT. Pretreatment of either superoxide dismutase or atorvastatin remarkably reversed these effects.nnnCONCLUSIONSnRLPs may suppress telomerase activity and accelerate EPC senescence through downregulating hTERT expression via the reactive oxygen species-dependent pathway.