The Relationship Between Oxidative Stress And Vascular Endothelial Injury And The Effect Of Probucol In Patients With Coronary Heart Disease

BackgroundVascular endothelial injury plays a critical role in the pathogenesis and progression of the coronary heart disease(CHD). A growing body of evidence suggests that endothelial dysfunction is associated with cardiovascular events.Oxidized low-density lipoprotein (ox-LDL) is thought to contribute to the endothelial dysfunction and pathogenesis of atherosclerosis,but the relationship of between the cardiac oxidative stress and acute coronary syndrome (ACS) were unclear.The antioxidant probucol has been proposed as a promising role against atherosclerosis and restenosis . The aim of study was to invertigate the cardiac oxidative stress ,vascular endothelial injury and their correlations to clinic manifestation in patients with stable angina(SA)or ACS .To explore the relation of the plasma ox-LDL level and endothelial flow mediated vasodilation (FMD) in ACS patients. The study tested the antioxidant probucol for vascular endothelial function in the patients of ACS after received 3 months therapy.MethodsThe 22 patients with AMI, 29 UA patients,25 SA patients and 20 subjects with normal coronary angiograms served as the control group were studied.In these patients,51 ACS patients were divided randomly into a routine treatment group(n=25)and a probucol treatment group(n=24).Probucol was administered once daily at a dose of 500mg. Oxidized low-density lipoprotein(ox-LDL), Nitric oxide (NO), and circulating endothelial cells (CEC) were measured in both coronary sinus and peripheral blood during percutaneous coronary intervention (PCI) .Nirtic oxide(NO)and Plasma ox-LDL was measured by spectrophotometer and Sandwich ELISE method, respectively. The plasma Hs-CRP levels were measured by using particle enhanced immunonephelometry. The brachial arterial hyperemia-induced flow mediated dilation (FMD) and sublingualnitroglycerin (NTG) mediated vasodilation were measured by high resolution ultrasound. These variables were analysed after received probucol 3 months.Results1 >The changes of NO and circulating CEC in patients with coronary heart disease: The level of NO in either coronary sinus or peripheral blood in patients with CHD was lower , AMI was lowest expecially, while the level of ox-LDL and CEC was markedly higher than those in the SA and control group (P < 0. 01 , P < 0. 05). In ACS patients , the level of NO in coronary sinus blood was lower ( P < 0. 05) , while the level of ox-LDL and CEC was higher ( P < 0. 01 , P < 0. 05) than those in peripheral blood. Similar differences appeared in patients with SA , but no siginificant difference between coronary sinus and peripheral blood was observed in the control group (P > 0. 05).2> The changes of brachial arterial endothelial dependent vasodilation reaction: The FMD in ACS group was significantly decrease compared to control group (P<0.05) , but NTG had no significantly difference between the two groups(P>0.05).The FMD had no significantly difference between the AMI and UA groups(P>0.05), but was significantly difference between the ACS and SA groups(P<0.05).3 -. The changes of the plasma ox-LDL level in patients with coronary heart disease: The level of ox-LDL in either coronary sinus or peripheral blood in patients with CHD was markedly higher than those in control group (P < 0. 05),In ACS patients , the level of ox-LDL in coronary sinus blood was higher than that in peripheral blood. (P < 0. 05) Similar differences appeared in patients with SA , but no siginificant difference between coronary sinus and peripheral blood was observed in the control group (P > 0. 05).4> The changes of the peripheral plasma Hs-CRP level in patients with coronary heart disease: The peripheral plasma Hs-CRP levels were significantly higher in CHD patients than those in the control subjects( P < 0.01) . The plasma Hs-CRP in ACS patients were higher than those in the SA patients( P<0.01). Similar differences appeared in patients with AMI and UA groups(P<0.01).5 > The correlation between oxidative stress ,Hs-CRP and endothelial dysfunction: The linear correlation analysis showed that plasma ox-LDLand Hs-CRP level was correlated positively with CEC,respectly (r =0.781,P<0.001, r = 0.776,P<0.001),but showed a negative correlation with NO (r =-0.592,P<0.001, r = -0.556,P<0.001) in patient with CHD.Plasma ox-LDL level was also positively correlated with Hs- CRP in patients with ACS (r = 0.778,P<0.001). Furthermore , By Logistic regression, the odds ratio (OR) of ox-LDL was > 1, that means ox-LDL is a risk factor; the OR of FMD was < 1.6> The level of NO in peripheral blood in patients with probucol treatment group was significantly increased compared to routine treatment group in ACS patients ( PO.01) ,while the level of CEC,ox-LDL,Hs-CRP was markedly desaesed (P < 0. 05 ,P < 0. 01, P<0.05).The FMD with probucol treatment group was significantly increased compared to routine treatment group(P<0.05).7, The level of NO in peripheral blood in patients with probucol treatnent group was significantly increased after 3 months compared to pretreamented (P<0.01), while the level of CEC,ox-LDL,Hs-CRP was markedly desaesed (P < 0. 01 ,P < 0. 01, P<0.05).The FMD with probucol treatment group was significantly increased compared to ACS routine treatment group(P<0.05).Conclusions:1 > Oxidized LDL not only plays an important role in coronary endothelial dysfunction ,but also contributes to the progress in the the acute coronary syndrome. Oxidative stress may be one of the pathophysiological basis of acute coronary event s.2^ The plasma ox-LDL was increased and FMD was decreased in the ACS patients. ox-LDL and endothelium-dependent vasodilation may be independent risk factor of ACS.3 > Oxidized low density lipoprotein and CRP may participate in endothelial dysfunction, which contributes to pathogenesis of the acute coronary syndrome.4> Antioxidative and antinflammation therapies were important strategy in clinical trearment of the acute coronary syndrome,but futher mechanisms were to study deeply in the furture.5> It was important that Vascular endothelial function and brachial arterial endothelial dependent vasodilation reaction may be improved in the ACS patients of after the antioxidant probucol theraphy .Probucol used in ACS clinical treatment may be available strategy.