The Effects And Mechanisms Of Probucol On Myeloperoxodase

BackgroundAcute coronary syndrome(ACS)is regarded as an acute inflammatory process.The systemic inflammatory factors such as Creactive protein(CRP),interleukin-18 are elevated in patients with ACS. Inflammation may contributed to the increased incidence of recurrent events after ACS.Monocyte is a critical cell in atherosclerotic inflammation.Monocytes are activated in peripheral blood and in disruptive plaques after ACS,and become the main resources of proinflammatory cytokine.Myeloperoxidase(MPO),which is largely abundant expressed in neutrophils and monocytes,may play an important role in atherosclerosis.Multiple lines of evidence suggest that the recruitment and activation of leukocytes,in particular neutrophils, release MPO.While the MPO expression and secretion of PBMs as well as its significance in patients with ACS is still unknown.Probucol is a potent antioxidant with modest lipid-lowering properties.Rencent studies suggested that probucol may also have antiinflammatory actions to explain it's antiatherosclerotic activity by reducing vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1.But the effect of probucol on MPO in patients with ACS is not clear. ObjectiveThe present study aimed to observe the effects of probucol on the expression of MPO in common aortic artery of hypercholesterolemic rabbits and investigate the effects of probucol on MPO expression in peripheral blood monocytes,meanwhile we investigated the effect of probucol on serum MPO and CRP levels in patients with ACS.MethodsThe concentrations of MPO in common aortic artery of hypercholesterolemic rabbits were measured by immunohistochemical study.Thirty-six individuals with acute coronary syndrome(ACS group) and 16 patients with stable coronary heart disease(CHD group)were enrolled in this study.PBMs were cultured and the supernatant were collected.The expression of myeloperoxidase in peripheral blood monocytes(PBMs)and concentrations of interleukin-18(IL-18)in supernatant in patients with ACS and CHD were compared.The effects of probucol on MPO expression in PBMs and IL-18 in supernatant of PBMs were also detected.The ACS individuals were then randomized to routine therapy group(group A,n=13)and treatment with probucol (10mg/d)group(group B,n=13)for 1 week.PBMs were isolated by gradient centrifugation.IL-18 levels in supernatant of PBMs were measured by enzyme-linked immunosorbent assays(ELISA).The expression of MPO in PBMs was detected by Western blot assay. Results1.Probucol significantly inhibited the MPO expression in common aortic artery of hypercbolesterolemic rabbits.2.Compared with CHD group,patients with ACS had increased MPO expression(1.12±0.11 vs 0.51±0.12,P＜0.01)by PBMs;IL-18 levels in supernatants of PBMs were markedly elevated(14.12±0.75 VS 11.50±0.79,P＜0.05);3.MPO expression was positively correlated with IL-18 levels in supernatants in patients with ACS(r=0.412,P=0.014),there were no correlation with plasma MPO and plasma CRP(r=0.176,p=0.112)and Gensini score(r=0.149,P=0.224).IL-18 levels in supernatants in patients with ACS were positively correlated with plasma CRP(r=0.623,P=0.003).4.probucol treatment in patients with ACS had a significant effect of decreasing MPO expression in PBMs,as well as reducing IL-18 levels in supernatants.5.Compared with CHD group,patients with ACS had increased plasma MPO concentrations,CRP as well as IL-18 levels;probucol treatment in patients with ACS had a significant effect of decreasing plasma MPO and CRP.Plasma MPO concentrations were no correlation with CRP,and were significantly correlation with FBS and FIB. Conclusions1.This study shows that peripheral blood monocytes in patients with ACS are activated,and the activation may be one of the causes which lead to increase plasma IL-18 levels.2.MPO is obviously expressed in PBMs from patients with ACS and further promote the secretion of IL-18 by PBMs.3.MPO play an important role in promoting inflammatory process in ACS.4.Probucol can reduce the MPO expression of PMBs following by decreasing IL-18 levels in supernatants of PBMs in patients with ACS. These findings suggest that probucol has anti- inflammatory effects in ACS,which are related to MPO.