Effects Of Transforming Growth Factor-β And CD40/CD40L On Atherosclerosis

Background and purpose:Many studies have confirmed that AS is a chronic inflammatory disease of avariety of immune factors are involved.Inflammation throughout the AS occurred, andthe development of the whole process of change, and determine the stability of the ASplaque. Research has shown that the CD40/CD40L system is widely expressed in ASplaque macrophages, smooth muscle cells, lymphocytes and endothelial cell surface.Their interactions significantly affected with AS related cell’s function,Such asadhesion molecules, cytokines, matrix metalloproteinases, tissue factor and so on.TGF-β1was inhibitting the inflammatory response of T cells, macrophages, NK cells, Bcells and other inflammatory cells, Inhibit matrix degradation of matrixmetalloproteinase flexibility protease, Increase the expression of early growth responsefactor, Improve the production of collagen,It was reducing the degradation of the matrix.Improve plaque stability by role of promoting fibrosis and anti-inflammatory.Methods:Specimens of human femoral artery atherosclerotic plaques were obtained from8patients undergoing artery endarterectomy and amputation surgery. They were dividedinto unstable plaque groups (with lipid core size＞40%) n=12and stable groups(with no or only little lipid core)n=12;the immunohistochemical staining wereperformed for TGF-β,CD40,CD40L.The distribution of the positive cells was observedunder the optical microscope, and optional10fields under high power microscope((10×40), total number of1000cells,count the number of positive cells, and calculatethe average.The independent samples T test were performed by using of the SPSS10.0statistical package, data were expressed as mean±standard error (SE). Results:1. HE staining: Unstable plaques: the lipid core size was greater than40%of theplaque size, the fibrous cap was also thinner, numerous foam cells and macrophageswere found within the plaque, and the endomembrane shedding was common. Stableplaques: the lipid core was﹤40%of the plaque size or absent, or calcific; The fibrouscap was thicker, and few foam cells or macrophages could be seen, endomembrane wasintegrity.2. TGF-β1Expression of in the shoulder, cap and basis of the plaque.I n the UPgroup, The base,fibrous cap, shoulder compared with the SP group, the correspondingparts of the expression was significantly reduced (P﹤0.05). The expression of TGF-β1in the shoulder region of unstable plaque was much lower than the basis and capregion(P﹤0.05).3. CD40Expression of in the shoulder, cap and basis of the plaque. An decreasedexpression of CD40was found in the stable plaque groups versus corresponding parts ofunstable ones (P﹤0.05). The expression of CD40in the shoulder region of unstableplaque was equal to the basis and cap region(P>0.05).4. CD40L Expression of in the shoulder, cap and basis of the plaque. Andecreased expression of CD40Lwas found in the stable plaque groups versuscorresponding parts of unstable ones (P﹤0.05). The expression of CD40L in theshoulder region of unstable plaque was much higher than the basis and cap region(P﹤0.05). We found a significant over-expression of CD40L in unstable plaque especiallyin the shoulder region.Conclusions:1. The shoulder region of the atheromatous plaque is tendency to thedestabilization.2. TGF-β can inhibit the development of atherosclerosis, stabilize the plaque.,It isa protective cytokine of atherosclerosis.3. The enhanced expression of CD40/CD40L in the shoulder region of unstableatherosclerotic plaques indicates They are important factors that contribute to plaqueinstability. CD40/CD40L can promote the occurrence and development ofatherosclerosis.