The Effects Of ICAM-1 Levels In The Atherosclerotic Rabbits By Short-term Usage Of Captopril

The molecular mechanism underlying atherosclerosis has beenstudied extensively in the last decade , and recent evidence hasindicated the importance of endothelium –monocyte interaction on theprogression of atherosclerosis . One early phase of atherosclerosisinvolves the recruitment of inflammatory cells from the circulationand their transendothelial migration. This process is predominantlymediated by cellular adhesion molecules, which are expressed on thevascular endothelium and on circulating leukocytes in response toseveral inflammatory stimuli. Selectins (P, E and L) and their ligands(mainly P-selectin ligand) are involved in the rolling and tetheringof leukocytes on the vascular wall. Intercellular adhesion molecules(ICAMs) and vascular cell adhesion molecules (VCAM-1), as well as someof the integrins, induce firm adhesion of inflammatory cells at thevascular surface, whereas platelet endothelial cellular adhesionmolecules (PECAM-1) are involved in extravasation of cells from theblood compartment into the vessel and underlying tissue. Among severaladhesion molecules, ICAM-1 is thought to be a key molecule whencirculating monocytes adhere to the endothelium and subsequentlytransmigrate into the intima. The intercellular adhesionmolecule-1(ICAM-1) is a member of the IG supergene family. ICAM-1 isexpressed on various cells like peripheral blood lymphocytes,endothelial cells and the cell surface form is supposed to be shedinto a soluble form. The expression of ICAM-1 is induced by cytokineslike interleukin-1, TNF-alpha or interferon-gamma. ICAM-1 isexpressed strongly on the endothelium overlying atheromatous plaquein human coronary and carotid arteries, hypercholesterolemic rabbits.The soluble form of CAMS, which lack the membrane spanning andcytoplasmic domains that are not present in the membrane bound forms,are found in the circulation. Although the functional significanceof CAMS in this form is not fully understood, there is evidence tosuggest that serum levels reflect tissue expression. In clinicalstudies, the level of soluble ICAM-1 (sICAM-1) has been shown to becorrelated with the degree of atherosclerosis , and more importantly,that sICAM-1 could be a predictor for future cardiovascular events .However, there is very little information about the levels of sICAM-1in an animal model of atherosclerosis. In terms of the involvementof ICAM-1 on atherosclerosis in animal models, The primary aim of thisstudy was to defined the importance of ICAM-1 in the formation andprogression of atherosclerosis and define if captopril can be a newdrug to CAD therapy.Methods: 1.Group:After abserved 1weeks ,Rabbits were randomly divided intotwo groups: (1)Cholesterol group(n=7): fed with 1% cholesterol dietfor 12 weeks, maintained 1.5% cholesterol diet for 4weeks;(2)Cholesterol+captopril treated group(n=7): fed with 1%cholesterol diet for 12 weeks ,1%cholestero diet supplemented bycaptopril (75㎎/㎏per day)for 4 weeks. And control group was fedwith normal diet for 16 weeks. 2. Measure of the serum lipids levels : At the end of 12 weeksand 16 weeks ,the blood were sampled from rabbits to measure the serumlipids levels by serum lipids analysis mechanism . 3.Measure of sICAM-1: Concentration of sICAM-1 in serum wasmeasured by using ABC-ELISA. 4.Observation of the aorter and measure of nuclear factor-κB inplaque: the aortas were harvested for histopathology observation andnuclear factor-κB immunohistochemistry analysis. 5.Statistical analysis: Numerical variable datas were expressedby X±s. The datas compared between two groups used analysis of t-test,more than two groups the analysis of variance and q-test were usedto compare differences by SPSS12.0 statistical software. P<0.01 thatmeant significant difference.Results:1. Rabbits fed with cholesterol-rich diet showed higher serum lipids(TC,LDL) levels﹙P<0.01) than those fed with normal diet for 16weeks. TG has no significant change. Treatment with captopril did not alter serum lipids levels .2. Rabbits fed with cholesterol-rich diet showed higher sICAM-1 levels(P<0.01)than those fed with normal diet for 16weeks. Treatment with captopril alter sICAM-1 levels significantly﹙ P <0.01).3. Histopathology and immunohistochemistry analysis : plaque can be seen in the aortas in rabbits fed with cholesterol-rich diet and nonexistent in control rabbits. Rabbits fed with captopril can be observed that the plaque in the aortas reduced significantly. The expression of the nuclear factor-κB can not be seen in control 34...