Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats.

BACKGROUND: Connexin43 (Cx43) is the predominant gap junction protein in heart and is involved in the control of cell-to-cell communication to modulate the contractility and the electrical coupling of cardiac myocytes. Left ventricular (LV) hypertrophy is accompanied by changes of Cx43 expression. Recent studies have demonstrated that statins reduced cardiac hypertrophy. However, it is unknown whether statins can affect Cx43 expression in hypertrophied left ventricular myocardium. This study was designed to assess the effects of atorvastatin on LV hypertrophy and Cx43 expression in spontaneously hypertensive rats (SHR). METHODS: Nine-week old SHRs were randomly divided into two groups. Some received atorvastatin at 30 mg/kg by oral gavage once daily for 8 weeks (SHR-A); others received vehicle. Age-matched Wistar-Kyoto rats (WKY) received atorvastatin or vehicle for 8 weeks were used as controls. At the end of the experiment, we investigated LV hypertrophy and the expression of Cx43 in LV myocardium in four groups. Cx43 expression was investigated by the methods of Western blotting, immunohistochemistry, and transmission electron microscope. LV hypertrophy was accessed by pathological analysis and plasma brain natriuretic peptide (BNP) level. RESULTS: LV hypertrophy was prominent in untreated SHR. In SHR, LV myocardium Cx43 level was upregulated, and the distribution of Cx43 was displaced from their usual locations to other sites at various distances away from the intercalated disks. After atorvastatin treatment, myocardium Cx43 level was reduced in SHR-A, and the distribution of Cx43 gap junction became much regular and confined to intercalated disk. Statins also prevented LV hypertrophy in SHR. CONCLUSIONS: These results provide novel in vivo evidence for the key role of Cx43 gap junctions in LV hypertrophy and the possible mechanism in anti-hypertrophic effect of statins. Atorvastatin treatment may have beneficial effects on LV hypertrophy in spontaneously hypertensive rats.

The safety and efficacy of oral anticoagulants with dual versus single antiplatelet therapy in patients after percutaneous coronary intervention: A meta-analysis.

BACKGROUND: A growing number of patients require oral anticoagulant (OAC) after undergoing percutaneous coronary intervention (PCI) with stent implantation due to the development of atrial fibrillation, but the optimal antithrombotic regimen remains controversial in these patients. METHODS: We systematically searched PUBMED, EMBASE, and CENTRAL from inception until September 2016 for randomized controlled trials or cohort studies that evaluated the comparative effects of TT versus DT. Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled by a random-effects model or a fixed-effects model. RESULTS: Twelve studies with a total of 30,823 patients were included in this analysis, including 6134 in the TT group and 24,689 in the DT group. No significant differences were found between the TT group and the DT group regarding major adverse cardiovascular events (MACE) (RR = 0.82, 95% CI: 0.58-1.17; I = 87.3%), stroke (RR = 1.08, 95% CI: 0.56-2.07; I = 65.5%), all-cause mortality (RR = 0.90, 95% CI: 0.54-1.51; I = 79.1%), or stent thrombosis (RR = 0.71, 95% CI: 0.41-1.24; I = 12.7%), and lower rates were observed for myocardial infarction (RR = 0.59, 95% CI: 0.50-0.70; I = 31.1%) and major bleeding with TT (RR = 0.86, 95% CI: 0.74-0.99; I = 24.3%). Meanwhile, we also found that compared with TT, OAC with clopidogrel treatment shows equal efficacy and safety outcomes. CONCLUSION: In patients on OAC undergoing PCI with stent implantation, compared with DT, TT shows equal effectiveness in terms of MACE, stroke, all-cause mortality, and stent thrombosis and lower risks of myocardial infarction and major bleeding. However, similar efficacy and safety outcomes were observed between the TT group and the OAC along with clopidogrel group.

Effects of aspirin on number, activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood.

AIM: To investigate whether aspirin has an influence on endothelial progenitor cells (EPC). METHODS: Total mononuclear cells (MNC) were isolated from peripheral blood by Ficoll density gradient centrifugation, then cells were plated on fibronectin-coated culture dishes. After 7 d of culture, attached cells were stimulated with aspirin (to achieve final concentrations of 1, 2, 5, and 10 mmol/L) for 3, 6, 12, and 24 h. EPC were characterized as adherent cells that were double positive for 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine low density lipoprotein (DiLDL) uptake and lectin binding by direct fluorescent staining. EPC proliferation and migration were assayed using a 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a modified Boyden chamber assay, respectively. An EPC adhesion assay was performed by replating the EPC on fibronectin-coated dishes, and then adherent cells were counted. In vitro vasculogenesis activity was assayed by using an in vitro vasculogenesis kit. Inducible nitric oxide synthase (iNOS) was assayed by Western blotting. RESULTS: Incubation of isolated human MNC with aspirin decreased the number of EPC. Aspirin also decreased the proliferative, migratory, adhesive, and in vitro vasculogenesis capacity of EPC, and also their iNOS levels in a concentration- and time-dependent manner. CONCLUSION: Aspirin decreases (1) the number of EPC; (2) the proliferative, migratory, adhesive and in vitro vasculogenesis capacities of EPC; and (3) iNOS levels in EPC.