ABSTRACT
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) homeostasis and plays a key role in acute coronary syndrome (ACS). The cardioprotective effect of PCSK9 inhibition extends beyond LDL cholesterol reduction, involving regulation of platelet function by not yet unraveled mechanisms. Oxidized-LDL (ox-LDL) is increased during ACS and induces platelet activation via binding to platelet surface. We will evaluate serum PCSK9 and its correlation with platelet reactivity and platelet-ox-LDL binding in Chinese ACS patients. METHOD AND DESIGN: In this pilot cross-sectional study, we will enroll 115 Chinese participants aged 30 to 75 years with ACS. Blood sample will be obtained after the first maintenance dose of aspirin and clopidogrel during morning time. Serum PCSK9 will be measured by an enzyme-linked immunoadsorbent assay. Platelet reactivity will be assessed by; Platelet activation (P-selectin and GPIIbIIIa expression using flow cytometry) and; Platelet aggregation using light transmission aggregometry in response to various stimuli. On-treatment platelet reactivity is measured by adenosine diphosphate-induced platelet aggregation. Binding of ox-LDL to platelet will be evaluated by flow cytometry. Spearman correlations will be used to determine association of serum PCSK9 with platelet functional parameters and platelet-ox-LDL binding. Additionally, continuous PCSK9 levels will be categorized into tertiles of equal size to investigate its association with on-treatment platelet reactivity. DISCUSSION: This study will reveal possible relationship between serum PCSK9 and platelet reactivity in the setting of ACS which may shed light on therapeutic potential in platelet inhibition by targeting PCSK9. The study will also explore the association of serum PCSK9 and platelet-ox-LDL binding, an important mechanism for platelet-LDL interplay, to provide mechanistic insight into PCSK9-mediated regulation of platelet reactivity.
Subject(s)
Acute Coronary Syndrome , Proprotein Convertase 9 , Humans , Cross-Sectional Studies , Cholesterol, LDLABSTRACT
AIM: Resveratrol(RSV) is an edible polyphenolic phytoalexin present in different plant species that plays an important role in improving endothelial dysfunction. However, the molecular mechanisms underlying these effects are unknown. In the present study, the mechanism underlying the protection of CRL-1730 cells by RSV against oxidative stress was examined. METHODS: We first assessed the effects of RSV on the cell viability and apoptosis of CRL-1730 cells exposed to hydrogen peroxide(H2O2). Real-time PCR was used to determine the microRNA-126(miR-126) expression in cells treated with RSV and/or H2O2. We also evaluated the PI3K/Akt signaling pathway in CRL-1730 cells following upregulation of the miR-126 expression. Finally, we determined the effects of miR-126 on RSV against oxidative injury using an miR-126 inhibitor. RESULTS: Treatment with RSV resulted in a significant increase in survival and a decrease in the apoptosis of CRL-1730 cells exposed to H2O2. We also found that H2O2 significantly suppressed the expression of miR-126, which was reversed by RSV in a dose-dependent manner. The overexpression of miR-126 decreased PIK3R2(p85-ß) and enhanced Akt phosphorylation, which resulted in an increase in the survival of CRL-1730 cells exposed to H2O2. More importantly, the downregulation of the miR-126 expression reversed the effects of RSV on the survival and apoptosis of CRL-1730 cells exposed to H2O2. In addition, the knockdown of Ets-1 reversed the effects of RSV on the miR-126 expression in CRL-1730 cells exposed to H2O2. CONCLUSIONS: In this study, we demonstrated that the protection of endothelial cells by RSV against oxidative injury is due to the activation of PI3K/Akt by miR-126.
Subject(s)
Apoptosis/drug effects , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells/pathology , Hydrogen Peroxide/pharmacology , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stilbenes/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Blotting, Western , Cell Proliferation/drug effects , Cells, Cultured , Flow Cytometry , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Oxidants/pharmacology , Oxidative Stress , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Resveratrol , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVE: To observe the therapeutic efficacy and safety of amiodarone combined with Shenmai Injection (å麦注å°æ¶²) on atrial fibrillation. METHODS: A total of 351 patients with atrial fibrillation caused by cardiovascular diseases and idiopathic atrial fibrillation were assigned to amiodarone group (control group, 128 cases) and amiodarone combined with Shenmai Injection group (treatment group, 223 cases). The patients in the control group received intravenous injection of 150 mg amiodarone in 10 min, followed by intravenous drip infusion at 1 mg /min and 6 h later at 0.5 mg /min until 48 h or cardioversion. The patients in the treatment group received the same treatment of amiodarone, while in addition, they received an injection of Shenmai Injection of 100 mL simultaneously. Blood pressure, ventricular rate, and cardioversion were observed. RESULTS: The total efficiency rate was 98% (control group) and 99% (treatment group) (P>0.05). The mean ventricular rate decreased 23% and 31% in the control group and the treatment group, respectively (P<0.05). The mean cardioversion time of the two groups was 570±211 min and 351±123 min, respectively (P<0.05). Only mild side effects were observed in both groups. CONCLUSION: Compared with amiodarone, amiodarone combined with Shenmai Injection takes effect more quickly with low side effects on the treatment of atrial fibrillation.