摘要：

mechanisms by which elevated BP leads to clinical vascular disease remain to be determined in future studies. Background: Previous studies in our laboratory have shown extensive leukocyte (neutrophil and monocyte/macrophage) migration from the adventitia into carotid arteries of ovariectomized (OVX) rats in the rst 24 hours after endoluminal injury that was inhibited by treatment with estrogen (E2). The current study tested the hypothesis that E2 inhibits expression of adhesion molecules, cytokines and chemokines that are chemoattractants for leukocytes in carotid arteries in the early hours following balloon injury. Methods: OVX rats treated with E2 (20 (cid:6) g/kg/day) or vehicle (V) were subjected to balloon injury of the right common carotid artery. 2 hours post-injury, arteries were harvested, 2–3 arteries were pooled, and RNA was extracted. Inammatory mediator mRNA was quantied using the SYBR green real-time RT-PCR method and normalized to ribosomal protein mRNA. Results: Normalized to OVX (cid:6) V injured as 100%, adhesion molecule (P-selectin, VCAM-1, ICAM-1), chemoattractant (CINC-2 (cid:3) and MCP-1) and pro-inammatory cytokine (IL-1 and IL-6) mRNA expression is up-regulated within 2 hours after endoluminal vascular injury and atten-uated by E2 treatment. At 24 hours, E2 still decreases P-selectin, IL-8, MCP-1and IL-6 but not VCAM or ICAM mRNA expression. No signif-icant effect of injury and E2 treatment was seen on the vasoprotective factor TGF- (cid:3) , and E2 did not alter mRNA expression of IL-10. Conclusion: Modulation of these markers may be a mechanism by which E2 limits the inammatory and neointimal response to endolumi- nal vascular injury. Purpose: Hypercholesteremia induces both functional and structural changes in the cardiovascular system including cardiac concentric re-modeling, impairment of the baroreex and endothelial dysfunction. The importance of inammatory processes in mediating the effects of cardiovascular risk factors, such as hypercholesteremia, is being increasingly recognized. This study examined whether hypercholesteremia induces a systemic inammatory responses that could play a role in the develop- ment of cardiovascular complications for Leukocytes and between Leukocytes were 5x106 cells per either and 5mM or with 10% bovine were used to measure phagocytosis of bodipy labeled, killed Staphylo- coccal or E. coli cells and production of phorbol ester induced radical oxygen species (ROS). Phagocytosis was measured by ow cytometry and ROS by uorescent conversion of dihydrorhodamine 123. Results: A signicant increase in ROS production was observed in leukocytes from blood of cholesterol fed animals relative to both control blood leukocytes and spleen cells from either set of animals (See Table ). The same trend was observed in the phagocytosis of E. coli bacteria and in endogenous uorescence of neutrophils. Conclusion: These studies indicate that hypercholesteremic animals had circulating leukcocytes with signicantly enhanced inammatory function. This pro-inammatory phenotype may play a role in the de-velopment of cardiovascular disease induced by hypercholesteremia. Our previous results demonstrate an immediate activation of NADPH oxidase in angiotensin II-stimulated phagocytes as well as in differenti-ated PLB-985 cells. Objective: The proposed study intends to determine the effect of superoxide radicals produced by angiotensin II-stimulated phagocytes on their adhesion to endothelial cells. Design and Methods: We established an in vitro co culture model of granulocyte-like PLB-985 or X-linked chronic granulomatus disease (X-CGD) PLB-985 cells with human EC in direct contact. Adhesion was measured by ow cytometry analysis. The cells were allowed to bind to EC for different periods of time at 37°C in a 5% CO 2 incubator. After mild trypsinization

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