ABSTRACT
Objective To investigate the effect of allicin on the development of atherosclerosis in apoE-/-mice and explore its underlying mechanism from the perspective of protein S-nitrosylation.Methods Thirty male apoE-/- mice were randomly divided into 3 groups:control group (saline,ig),low-dose group (allicin,9 mg/kg·d, ig)and high-dose group (allicin,18 mg/kg·d,ig).They were fed with high cholesterol diet for 12 weeks.The levels of plasma lipids,oxidized-LDL (ox-LDL),malondialdehyde,tumor necrosis factor-alpha and nitric oxide (NO)were measured.The atherosclerotic lesions in aortic root were evaluated after hematoxylin and eosin staining and elastica van Gieson and immunohistochemical staining,respectively.Furthermore,in vitro experiments were performed using human umbilical vein endothelial cells (HUVECs).The HUVECs were treated with allicin (10μmol/L or 20 μmol/L)for 24 hours in the presence of ox-LDL (50 μg/mL).The level of NO in supernatant was measured by a nitrate/nitrite assay. The protein S-nitrosylation of the HUVECs was detected through immunofluorescence.Results The histological analysis revealed that allicin treatment not only significantly decreased the areas of the atherosclerotic lesion (all P <0.05)but also suppressed the macrophage accumulation and smooth muscle cell proliferation in the lesion.There was no significant difference in the levels of plasma lipids between control and treated groups.However,allicin exerted obvious anti-oxidative and anti-inflammatory effects. Interestingly,the allicin treatment led to marked increase of the plasma NO level (P <0.05)and aortic protein S-nitrosylation.The experiments in vitro further proved that the allicin up-regulated the levels of NO and protein S-nitrosylation in HUVECs treated with ox-LDL (P < 0.01 ).Conclusion Allicin can inhibit the development of atherosclerosis.The mechanism is associated with the up-regulation of protein S-nitrosylation in endothelial cells, which plays an important role in anti-oxidization and anti-inflammation.
ABSTRACT
ABSTRACT:Objective To analyze the correlation between plasma nitric oxide (NO)level and atherosclerotic lesion in high cholesterol-fed (HCD ) rabbits.Methods Twenty male Japanese white rabbits were divided randomly into two groups,which were fed with normal diet (control group,n =10)or HCD (experimental group, n =10 )for 1 6 weeks.At the end of the experiment,plasma lipid and NO levels were measured.The gross atherosclerotic lesions in each group were detected by Sudan IV staining while intimal lesion area was measured by hematoxylin/eosin (HE)and elastica van gieson (EVG).Moreover,the macrophages (MΦ)and smooth muscle cells (SMC)were detected by immunohistochemical staining.The correlation analysis was made to reveal the relationship between atherosclerotic lesions and plasma NO level.Results Compared with those in control group, the total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C)and NO levels all increased significantly in experimental group.Atherosclerotic lesions appeared on the vascular wall in the latter group.The area of atherosclerotic lesions and MΦ in the plaque had a positive association with plasma NO level. Conclusion There is a relationship between plasma NO level and the size of HCD-induced atherosclerotic lesions in rabbits.Meanwhile,the MΦ positive area in the atherosclerotic plaque is also associated with plasma NO level in cholesterol-fed rabbits,suggesting that plasma NO level may be associated with the occurrence and progress of early atherosclerosis.