ABSTRACT
Ezetimibe was reported to pharmacologically defend against oxidative stress.This study was designed to investigate whether ezetimibe can protect against the oxidative stress induced by oxidized low-density lipoprotein (oxLDL) in vitro and the underlying mechanism.Human umbilical vein endothelial cells (HUVECs) were pretreated with ezetimibe and then exposed to oxLDL for 24 h.TUNEL assay and detection for the protein levels of cleaved caspase-3,Bcl-xl and Bcl-2 were employed to assess the oxLDL-induced endothelial apoptosis.Intracellular reactive oxygen species (ROS) generation was evaluated by measuring dichlorofluorescein (DCF) fluorescence.The activities of endothelial antioxidant enzymes [superoxide dismutase (SOD) and catalase] were tested via an enzymatic assay.The mitochondrial membrane potential (MMP) was monitored by flow cytometry using JC-1 staining.Phosphorylation levels of glycogen synthase kinase-3β (p-GSK-3β) and Akt (p-Akt),as well as total GSK-3β and Akt were determined by Western blotting.The results showed that ezetimibe treatment inhibited HUVECs apoptosis,intracellular ROS production,and enhanced antioxidant enzyme activities elicited by oxLDL.HUVECs exposed to oxLDL alone had reduced mitochondrial function,while ezetimibe pre-intervention could significantly rescue the MMP.Furthermore,the protein levels of p-GSK-3β and p-Akt in ezetimibe-pretreated HUVECs were markedly increased as compared with those in oxLDL-induced HUVECs.However,no significant effect on total GSK-3β and Akt was found in ezetimibe-pretreated HUVECs.Taken together,it was concluded that ezetimibe protects against oxLDL-induced oxidative stress through restoring the MMP,which may be mediated by Akt-dependent GSK-3β phosphorylation.
ABSTRACT
Ezetimibe was reported to pharmacologically defend against oxidative stress.This study was designed to investigate whether ezetimibe can protect against the oxidative stress induced by oxidized low-density lipoprotein (oxLDL) in vitro and the underlying mechanism.Human umbilical vein endothelial cells (HUVECs) were pretreated with ezetimibe and then exposed to oxLDL for 24 h.TUNEL assay and detection for the protein levels of cleaved caspase-3,Bcl-xl and Bcl-2 were employed to assess the oxLDL-induced endothelial apoptosis.Intracellular reactive oxygen species (ROS) generation was evaluated by measuring dichlorofluorescein (DCF) fluorescence.The activities of endothelial antioxidant enzymes [superoxide dismutase (SOD) and catalase] were tested via an enzymatic assay.The mitochondrial membrane potential (MMP) was monitored by flow cytometry using JC-1 staining.Phosphorylation levels of glycogen synthase kinase-3β (p-GSK-3β) and Akt (p-Akt),as well as total GSK-3β and Akt were determined by Western blotting.The results showed that ezetimibe treatment inhibited HUVECs apoptosis,intracellular ROS production,and enhanced antioxidant enzyme activities elicited by oxLDL.HUVECs exposed to oxLDL alone had reduced mitochondrial function,while ezetimibe pre-intervention could significantly rescue the MMP.Furthermore,the protein levels of p-GSK-3β and p-Akt in ezetimibe-pretreated HUVECs were markedly increased as compared with those in oxLDL-induced HUVECs.However,no significant effect on total GSK-3β and Akt was found in ezetimibe-pretreated HUVECs.Taken together,it was concluded that ezetimibe protects against oxLDL-induced oxidative stress through restoring the MMP,which may be mediated by Akt-dependent GSK-3β phosphorylation.
ABSTRACT
Objective To systematically review the effects of intracoronary microcatheter agents in the treatment of patients with no-refl ow phenomenon. Methods Databases including Medline, EMbase, the Cochrane Library, CBM, CNKI, VIP and WanFang Data were searched electronically f rom inception to April 2017 for randomized controlled trials (RCTs) about intracoronary agents for no-reflow phenomenon. Two reviewers independently screened literatures, extracted data and assessed the risk of bias of the studies included. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 8 RCTs involving 424 patients were included. The results of Meta-analysis showed that the microcatheter group had significantly better TIMI flow grade[RR=0.38,95%CI(0.27,0.52), P<0.000 01],TIMI myocardial perf usion grade[RR=0.35,95%CI(0.23,0.55),P<0.000 01],corrected TIMI f rame count[MD=-9.99,95%CI(-13.22,-6.76)P<0.000 01]and hypotension[RR=0.57,95%CI(0.35, 0.90),P=0.02] than those of the guiding catheter group. There was no statistical difference between the two groups in short period major adverse cardiovascular events and left ventricular ejection fraction.Conclusions Current evidence shows that intracoronary microcatheter agents could improve blood flow in patients with no-reflow phenomenon and has good safety. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be verified by carrying out more high-quality RCTs.
ABSTRACT
The clinical characteristics of painless aortic dissection were investigated in order to improve the awareness of diagnosis and treatment of atypical aortic dissection. The 482 cases of aortic dissection were divided into painless group and pain group, and the data of the two groups were retrospectively analyzed. The major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%) had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes, smoking and drinking history had no statistically significant differences between the two groups (P>0.05). The proportion of Stanford type A in painless group was significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The incidence of unconsciousness in the painless group was significantly higher than that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension in painless group was significantly higher than that in pain group for 4.26 folds (P=0.01). Computed tomography angiography (CTA) examination revealed that the incidence of aortic arch involved in the painless group was significantly higher than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that the incidence of painless aortic dissection was higher in Stanford A type patients, commonly seen in the patients complicated with hypotension and unconsciousness. CTA examination revealed higher incidence of aortic arch involvement.
ABSTRACT
The clinical characteristics of painless aortic dissection were investigated in order to improve the awareness of diagnosis and treatment of atypical aortic dissection. The 482 cases of aortic dissection were divided into painless group and pain group, and the data of the two groups were retrospectively analyzed. The major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%) had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes, smoking and drinking history had no statistically significant differences between the two groups (P>0.05). The proportion of Stanford type A in painless group was significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The incidence of unconsciousness in the painless group was significantly higher than that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension in painless group was significantly higher than that in pain group for 4.26 folds (P=0.01). Computed tomography angiography (CTA) examination revealed that the incidence of aortic arch involved in the painless group was significantly higher than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that the incidence of painless aortic dissection was higher in Stanford A type patients, commonly seen in the patients complicated with hypotension and unconsciousness. CTA examination revealed higher incidence of aortic arch involvement.