| Background: Atherosclerosis is a chronic inflammation of artery. As the important inflammatory signaling, CD40-CD40 ligand(CD40L) system may be the key link to promote atherosclerosis. The effects of inhibition of CD40-CD40L on atherosclerosis are given more and more attention. But it is uncertain if inhibition of CD40 signaling could alleviate atherosclerosis and enhance stability of the plaque.Objective: To evaluate the effects of inhibition of CD40-CD40L system by anti-CD40L antibody on atherosclerosis in apoE gene knockout mice and provide new clues for prevention and treatment of atherosclerosis. Methods: 8-week-old male apoE gene knockout mice were divided into untreated control group(n=10) and anti-CD40L antibody group(n=8, 250ug/0.SmL, intraperitoneal injection twice a week). Mice had been fed on western diet and treated for 16 weeks. Serum lipid, soluble vascular cell adhesion molecule-l(sVCAM-1) and soluble intercellular adhension molecule-l(sICAM-1) were deteced. The aortas were taken for histomorphometry observation. The positive percentage of macrophage cells, smooth muscle cells were determined by immunohistochemistry, and. the expression of matrix metalloproteinase-9(MMP-9) were mensurated by Western blotting.Results: Anti-CD40L treatment could lower sVCAM-1 and sICAM-1 (P＜0.01), It had no impact on serum lipid. Compared with untreated control group, anti-CD40L group showed a reduction in plaque area, ratio of plaque/intimal area, vascular thickness(P＜0.05). Inhibition CD40-CD40L also could reduce the amount of macrophage cells, increase the amount of smooth muscle cells (P＜0.05). The expression of MMP-9 decreased in anti-CD40L antibody group (P＜0.01), and the lesions were more stable.Conclusions: Inhibition of CD40-CD40L could decrease vascular inflammation, prevent development of atherosclerosis, and make the lesions more stable. It had no effect on serum lipid. Background: Platelet is a kind of flammatory cell which plays an important role in atherosclerosis. Recent studies have demonstrated that anti-platelet drugs could inhibit progression of the plaque, but the mechamism is not clear. Inhibition of CD40-CD40 ligand(CD40L) system could alleviate atherosclerosis and enhance stability of the plaque, which has been demonstrated in the first part of this study. But it is uncertain if anti-platelet drugs could obstruct CD40-CD40L system by inhibiting activation of platelet, and attenuate the progression of atherosclerosis.Objective: To evaluate the effects of aspirin and clopidogrel on inhibiting the development of atherosclerosis, and on CD40-CD40L system in apoE gene knockout mice.Methods: 8-week-old male apoE gene knockout mice were divided into untreated control group(n=10), aspirin group(n=10, 58mg/kg.d-1, gastric gavage), clopidogrel group(n=10, 14mg/kg.d-1, gastric gavage), aspirin combined with clopidogrel group(n= 10, aspirin 58mg/kg.d- 1, clopidogrel 14mg/kg.d-1, gastric gavage). Mice had been fed on western diet and treated for 16 weeks. Serum lipid , soluble vascular cell adhesion molecule- 1 (sVCAM- 1), soluble intercellular adhension molecule-l(sICAM-1), soluble CD40L(sCD40L), and expression of CD40L on platelets were deteced. The aortas were taken for histomorphometry observation. The positive percentage of macrophage cells, smooth muscle cells, and CD40L were determined by immunohistochemistry.Results: Aspirin and clopidogrel could lower level of sVCAM-1 and sICAM-1 (P＜0.05). Compared with untreated control group, aspirin group, clopidogrel group, and combined group showed a reduction in plaque area, ratio of plaque/intimal area, vascular thickness(P＜0.05). They also reduced the amount of macrophage cells, increase the amount of smooth muscle cells (P＜0.05). Clopidogrel had more effect on reduction of sCD40L and inhibition of expression of CD40L on platelets and in plaques than aspirin (P＜0.05), but in other ways no significant differences were existed between clopidogrel group and aspirin group (P＞0.05). Howerer, the combination of aspirin and clopidogrel had better effect than aspirin or clopidogrel alone (P＜0.05).Conclusions: Aspirin and clopidogrel could inhibit inflammation, prevent the development of atherosclerosis, and make the lesion more stable through inhibition of CD40-CD40L system. Their combination showed synergic effects. Background: Anti-platelet drugs and inhibition of CD40 signaling with anti-CD40 ligand(CD40L) antibody could attenuate atherosclerosis. However, atherosclerosis results from complex interactions among multiple genetic and environmental facors. So simplex treatment is not optimal, and combined treatment could be more effective.Objective: To evaluate the effects of combined anti-platelet drugs with anti-CD40L antibody on inhibiting the development of atherosclerosis in apoE gene knockout mice.Methods: 8-week-old male apoE gene knockout mice were divided into untreated control group(n=10), anti-platelet drugs group(n=10, aspirin 58mg/kg.d-1+clopidogrel 14mg/kg.d-1, gastric gavage), anti-CD40L antibody group(n=8, 250ug/0.5mL, intraperitoneal injection twice a week), combined group(n=9, aspirin 58mg/kg'd-1 and clopidogrel 14mg/kg·d-1, gastric gavage + antioCD40L antibody, 250ug, intraperitoneal injection twice a week). Mice had been fed on western diet and treated for 16 weeks. Serum lipid, soluble vascular cell adhesion molecule- 1 (sVCAM- 1), soluble intercellular adhension molecule-l(sICAM-1) were deteced. The aortas were taken for histomorphometry observation. The positive percentage of. macrophage cells, smooth muscle cells were determined by immunohistochemistry, and the expression of matrix metalloproteinase-9(MMP-9) were mensurated by Western blotting. Results: Antiplatelet treatment and anti-CD40L treatment could lower serum sVCAM- 1 and sICAM-1 (P<0.01). Compared with untreated control group, antiplatelet group, anti-CD40L antibody group, and combined group showed a reduction in plaque area, ratio of plaque/intimal area, vascular thickness(P＜0.05). They also reduced the amount of macrophage cells, increase the amount of smooth muscle cells (P＜0.05). It had no impact on serum lipid (P＞0.05). Combination of antiplatelet drugs and anti-CD40L antibody had better effect(P＜0.05). The expression of MMP-9 decreased in anti-CD40L antibody group and combined group(P＜0.01). Antiplatelet treatment had not this effect. Conclusions: Antiplatelet treament and anti-CD40L antibody could decrease vascular inflammation, prevent development of atherosclerosis, and make the lesions more stable. Their combination had better effect.
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