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Objective To evaluate the effects of probucol combined with atorvastatin medication on blood levels of oxidized low-density lipoprotein (ox-LDL), lipoprotein-associated phospholipase A2 (Lp-PLA2), and the correlation of their changes in patients with acute coronary syndrome (ACS) undergoing percutaneous poronary intervention (PCI). Methods A total of 97 patients with ACS and undergoing PCI were randomly divided into two groups according to the date of admission:single medication group (n=42),the patients were taken atorvastatin 20 mg/d; and combined medication group (n=55),the patients were taken atorvastatin 20 mg/d with probucol 500 mg/d. The plasma levels of ox-LDL and Lp-PLA2 were measured in both groups before and 6-8 weeks after the medication. Then the results were compared and analyzed between two groups. Results (1) Before treatment there were no significant differences in levels of ox-LDL and Lp-PLA2 between two groups (P>0.05). After the treatment, the ox-LDL level was significantly decreased in combined medication group (P<0.01). After the treatment, the levels of Lp-PLA2 were significantly decreased than those before treatment in both groups (P<0.01). Compared with single medication group, levels of ox-LDL and Lp-PLA2 were significantly lower in combined medication group (P < 0.01). (2) After treatment, the absolute value of Lp-PLA2 decline (ΔLp-PLA2) was positively correlated with the absolute value of ox-LDL decline (Δox-LDL) in combined medication group (r=0.314, P=0.020). Conclusion Probucol combined with statin therapy can reduce ox-LDL and Lp-PLA2 levels, and with a positive correlation between them. Probucol can further decrease the level of Lp-PLA2 by inhibiting ox-LDL production, which may be one of the mechanisms of its anti-atherosclerosis.
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Objective: To observe the effect of oxidative-low density lipoprotein (ox-LDL) injured human leukemia mononuclear cells (THP-1) adhesion to human umbilical vein endothelial cells (HUVECs)in vitrowith the intervening function of dredging collateral drug, tongxinluo (TXL) and ginsenoside (Rb1). Methods: Cell injury was induced by ox-LDL treatment. The cells were divided into 4 groups:①Normal control group,②Injury model group, the cells were cultured by ox-LDL,③TXL group, the cells were cultured with both ox-LDL and TXL,④Rb1 group. HUVEC viability was measured by MTS assay, adherence rate of THP-1 cells to HUVECs was tested by vital cell staining. The contents of monocyte chemoat-tractant protein (MCP-1), soluble vascular cell adhesion molecule (sVCAM-1), soluble inter vascular cell adhesion molecule-1 (sICAM-1) and E-selectin in HUVEC conditioned medium were detected by ELISA; protein expressions of CCR2, VLA4 and Mac-1 in THP-1 cells were examined by Western blot analysis. Results: Compared with Control group, HUVEC viability was decreased in Injury model group (100 ±1.31) % vs(75.57 ± 1.02) %, while increased in both TXL and Rb1 groups (99.25 ± 1.40) % and (99.48 ± 2.15) %; Injury model group showed elevated adherence rate of THP-1 cells to HUVECs, while the adherence rates were reduced in both TXL and Rb1 groups. Compared with Injury model group, TXL group and Rb1 group showed decreased levels of MCP-1, sVCAM-1, sICAM-1 and E-selectin in HUVEC conditioned medium; decreased protein expressions of CCR2, VLA4 and Mac-1 in THP-1 cells. Conclusion: TXL and Rb1 could protect HUVECs, reduce ox-LDL injury induced vascular endothelial cell adhesion and decrease relevant receptor expression in monocytes; therefore, inhibit injured monocytes adherence to vascular endothelial cells.
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Aim To investigate the mechanism for the inhibitory effect of hydrogen sulfide on the expression of tissue factor(TF)induced by oxidative low-density lipoprotein(ox-LDL)in endothelial cells.Methods Human umbilical vein endothelial cells (HUVECs ) were treated with 50 mg·L-1 ox-LDL in the absence or presence of different concentrations of NaHS (25 , 50,100 and 200 μmol·L-1 )for 24 h.The mRNA expression and protein content of TF in HUVECs were determined by reverse transcription PCR and ELISA, respectively.The content of intracellular reactive oxy-gen species (ROS)was determined by DCFH,an oxi-dative sensitive fluorescent indicator.The activation of nuclear factor-kappaB (NF-κB)was estimated by its expression in nuclear extracts analyzed by Western blot.Results Ox-LDL induced TF mRNA expression and increased TF protein content in HUVECs.The in-crease in intracellular ROS production and the activa-tion of NF-κB were observed in HUVECs treated with ox-LDL.However,NaHS could markedly inhibit the increases in TF mRNA and protein levels induced by ox-LDL.Also the elevation of intracellular ROS pro-duction and the activation of NF-κB elicited by ox-LDL were significantly suppressed by pretreatment with NaHS.In addition,pretreatment with BAY 1 1-7082 (10 μmol·L-1 ),the inhibitor of NF-κB or N-acetyl-L-cysteine(1 mmol·L-1 ),an antioxidant,could also decrease the TF mRNA and protein level as well as ROS production and NF-κB activation induced by ox-LDL in HUVECs,similar to the effects of 200 μmol· L-1 NaHS.Conclusion The mechanism for the in-hibitory effect of H2 S on the ox-LDL- induced TF ex-pression in endothelial cells may be related to inhibi-ting intracellular ROS production and subsequently NF-κB activation.
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Objective To investigate the relationship between the oxidized low-density lipoprotein(ox-LDL) in the blood from the coronary sinus and impaired endothelium-dependent vasodilation in patients with coronary artery disease(CHD).Methods Four groups of patients were subjected,including acute myocardial infarction group(AMI,n=22),unstable angina group(UA,n=29),and stable angina group(SA, n=25) and control group(n=20) who was first suspected as CHD and then verified with normal coronary angiograms.Blood form the coronary sinus was collected through cardiac cathetering and the ox-LDL level was measured by Sandwich ELISA method.Brachial arterial hyperemia-induced flow mediated dilation(FMD) and sublingual nitroglycerin(NTG) mediated vasodilation were measured by high resolution ultrasound.Results The blood level of ox-LDL in patients with CHD was markedly higher than those in control group(P