Expression and Location of Intracellular Tissue Factor in Atherosclerosis Stable Plaque of ApoE^(-/-) Mice

In the ApoE^-/- mouse model of atherosclerosis （AS） stable plaque, the expression and location of intracellular tissue factor （TF） in the cellular components of AS stable plaque were investigated in order to explore the cellular mechanism of AS thrombosis. Pathological changes of the stable plaque were observed under a microscope. The expression of TF protein was examined in aortic stable plaque of mice by using immunohistochemistry. Color image planimetric system was used to analyze the histological components of the stable plaque and the TF distribution. Under the confocal microscope, the intracellular TF location in the stable plaque of mice was observed. The results showed the cellular area was the major part of stable plaque （67.36%±6.52%, P〈0.01）. The percentage of total area occupied by cellular area was significantly larger than atheromatous gruel and acellular area （P〈0.01）. Macrophages and smooth muscle cells （SMC） were major cells in the cellular area. The percentage of total area occupied by SMC was significantly larger than by macrophages （P〈0.01）. Multiple linear regression analysis showed there was a positive correlation between TF area and SMC area （r=0.616, P=-0.008）, and no correlation was found between TF area and macrophage area （r=0.437, P=0.08）. Pictures of color image planimetric analysis of TF and SMC were merged to highlight areas with co-localization （yellow）, it was concluded that the process could be a cell-mediated TF expression in the stable plaque. SMC may be the major source of TF in AS without plaque rupture.

The Thromboxane Receptor Antagonist S18886 influence the stability of atherosclerosis in ApoE Null Mice

Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clopidegrol on the development of atherosclerosis, accumulation of lipid- filled macropha-ges in apoE null mice. Methods All mice were done cuffed common carotid artery and fed a Western-type atherogenic diet for 6 weeks from the day of surgery, at same time the therapy group mice were gavaged S18886 5 mg/Kg/day and clopidegrol respec- tively, the same volume water were gavaged as the placebo group. Results profound inhibition of lesion area growth after cuff of the right common carotid artery in mice with 5 mg/kg of S18886, markdely reduce intima to media ratio and intima to total wall area compare with clopidegrol or blank group; Macrophage infiltration into sites of arterial plaque was also markedly attenuated by ICAM-1 deficiency in the S18886 group, whereas inside the arterial wall plaque of placebo apoE null mice α-smooth muscle actin markedly attenuated. Treatment with 25 mg/kg/day clopidegrol reduced the level of ICAM-1 stai ning, both S18886 and clopidegrol didn't influence the α-smooth muscle actin inside plaque. Conclusions It was considered that the novel anti-thrombotic drug significant reduce macrophage infiltration in the sites of arterial plaque by ICAM-1 deficiency, S18886 not only reduce the size, but also stabilized the plaque.

Correlation between FcγRⅢA and Aortic Atherosclerotic Plaque Destabilization in ApoE Knockout Mice and Intervention Effects of Effective Components of Chuanxiong Rhizome and Red Peony Root

Objective： To explore the correlation between Fc γ R IIIA （CD16A） and aortic atherosclerotic plaque destabilization in apoE knockout （apoE KO） mice and the intervention effects of effective components of Chuanxiong Rhizome and Red Peony Root. Methods： Eight 8-week-old male C57BL/6J mice were selected as the control group. Forty 8-week-old male apoE KO mice were randomly divided into the model group, apoE KO ＋ intraperitoneal injection immunoglobulin group （IVIG）, apoE KO ＋ simvastatin group （Sm）, apoE KO ＋ high dosage of Xiongshao Capsule （XSC,芎芍胶囊） group （XSCH）, and apoE KO ＋ low dosage of XSC group （XSCL）, 8 mice in each group. Mice in the control group were put on a normal diet, and others were fed with a high-fat diet. After 10-week different interventions, monocyte CD16 expression was detected by flow cytometry, aortic matrix metalloproteinase-9 （MMP-9） mRNA expression was detected using reverse transcription- polymerase chain reaction, and serum tumor necrosis factor （TNF）-a level was detected using enzyme-linked immunosorbent assay. Results： Compared with the control group, monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-a level in the model group increased obviously （P〈0.01）. Injections of apoE KO mice with intraperitoneal immunoglobulin during a 5-day period significantly reduced the monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-a level （P〈0.01 or 0.05） over a 10-week period of high-fat diet. Indices above in the Sm group, XSCH group, and XSCL group decreased in a different degree. Of them, the aortic MMP-9 mRNA expression in XSCH group was lower than that in Sm group （P〈0.05） and the monocyte CD16 expression and serum TNF-a level showed no significant difference between XSCH group and Sm group （P〉0.05）. Correlation analyses suggested positive correlation between monocyte CD16 expression and aortic MMP-9 mRNA expression or serum TNF-a level in IVIG group, XSCH group, and XSCL group. Conclusions： Fc γ/R IliA mediates systemic inflammation in the progression of coronary heart disease with blood stasis syndrome. XSC could stabilize atherosclerotic plaque by suppressing inflammation and its target was relative with Fc γ RIIIA.