The roles of CD40-CD40L in carotid atherosclerotic plaque stability and their correlation with matrix metalloproteinase 9 / 中华神经科杂志

ABSTRACT

Objective To investigate the expression of CD40,CD40L and MMP9 in carotid atherosclerotic plaques and evaluate their roles in carotid atherosclerotic plaque stability.Methods Carotid atherosclerotic plaques were isolated in carotid eversion endarterectomy (GEE) in 37 patients with high-grade stenosis (>70%) including 20 stroke (A group) and 17 non-stroke patients (B group).The control group included samples of normal carotid artery from 11 normal individuals,The RNA expression levels of CD40,CD40 L and MMP9 in all A,B and control groups were quantitatively detected by real-time quantification polymerase chain reaction (PCR) and the protein expression levels were detected by Western blotting analysis.The expression and distribution of CD40,CD40L and MMP9 in carotid atherosclerotic plaques were detected by immunohistochemistry staining.Then correlations between CD40-CD40L and MMP9 were statistically analyzed.Results The relative CD40 mRNA level in high-grade stenosis of A group,B group and normal control were 2.41±0.43,1.03±0.38 and 0.31±0.12,respectively,and MMP9 mRNA 6.88±1.57,1.90±0.44 and 0.39±0.12,respectively.The levels of CD40 and MMP9 mRNA in A group were significantly higher than those in B group (P=0.000),the levels of CD40 and MMP9 in B group were significantly higher than those in controls (P=0.000).There was a linear correlation between CD40 and MMP9 mRNA (r=0.929,P=0.000).However,there were no significantly difference in mRNA levels of CD40L between carotid atherosclerosis and controls.The protein expression levels of CD40,CD40L and MMP9 in A group were significantly higher than those in B group (FCD40=104.100,P=0.000;FCD40L=129.932,P=0.000;FMMP9=13.565,P=0.021) and B group higher than normal controls (FCD40=115.848,P = 0.000;FCD40L= 30.482,P=0.005;FMMP9=35.557,P=0.004).The areas of positive staining of CD40,CD40L and MMP9 in immunochemistry study in A group were significantly higher than those in B group and B group was significantly higher than controls.There were linear correlations between positive staining areas Of CD40 and CD40L,CD40 and MMP9,CD40L and MMP9 (r=0.963,0.959,0.929,P=0.000).Expressions of CD40,CD40L and MMP9 were significantly higher in the shoulder areas of the atherosclerotic plaques than in other areas.Conclusions The CD40-CD40L has an important role in the formation of carotid atherosclerosis and plaque instability,probably by up-regulating MMP9.The expression of CD40L may be regulated by post-transcriptional modification to exert biological effects.