SYMPATHETIC NERVOUS SYSTEM REGULATION OF CELL ADHESION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 高血压影响着5000多万美国人，每年带来巨大的经济和社会成本。 高血压与中风和动脉粥样硬化的风险显著增加相关。除了血压升高外，高血压的特征还包括神经内分泌和免疫激活以及细胞粘附分子激活，包括C反应蛋白（CRP）、炎症细胞因子白细胞介素-6（IL-6）和肿瘤坏死因子-α水平升高（TNF-α）和可溶性粘附分子细胞间粘附分子-1（sICAM-1）（CD54）和E-选择素（sCD62 E），它们是发病率和死亡率结果的预测因子。高血压的药物治疗成功地降低了血压，但对减少伴随的炎症及其相关的发病率和死亡率的有效性有限。运动和饮食干预已被证明可以显着降低血压，但很少有研究检查高血压炎症或潜在机制的影响。我们将在150例目前未服用抗高血压药物的高血压患者（血压140/90 mm Hg，但120/80 mm Hg，但140/90 mm Hg）中检查12周运动干预和12周运动加饮食干预对炎症和细胞粘附的影响。在干预前后，我们将评估静息和应激诱导（精神应激和平板运动试验）的CRP、IL-6、TNF-α、sICAM-1、sE-选择素循环水平的变化，白细胞上2-整合素亚基CD11a和CD11b的表达，白细胞活化（伪足形成）和外周血单核细胞（PBMC）趋化性。 假设1.与12周的等待名单对照组相比，12周的运动干预，特别是12周的运动加饮食干预，将减少休息和应激诱导的炎症和细胞粘附。 1-1.与等待名单对照组相比，干预组将表现出CRP、IL-6、TNF-α、sICAM-1、sE-选择素、白细胞CD 11a和CD 11b表达、白细胞活化、静息时的趋化性水平降低。 1-2.与等待名单对照组相比，干预组将表现出CRP、IL-6、TNF-α、sICAM-1、sE-选择素、白细胞CD11a和CD11b表达、白细胞活化和趋化性水平降低，以响应干预前后的急性激发。 假设2.与12周的等待名单对照组相比，12周的运动干预，特别是12周的运动加饮食干预，将提高健康水平，降低尿儿茶酚胺和皮质醇水平，并提高胰岛素敏感性。[这些假设的影响，虽然相对简单和预期的，需要验证，以测试在假设3中提出的机制。 2.1与等待名单对照组相比，运动组和运动加饮食组都会显示出更高的健康水平。 2.2与等待名单对照组相比，运动组和运动加饮食组都将显示出增加的胰岛素敏感性和降低的儿茶酚胺和皮质醇水平。 2.3与运动干预组或等待名单对照组相比，运动加饮食组将显示出更大的体重减轻。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypertension affects more than 50 million Americans and comes with enormous annual economic and social costs. Hypertension is associated with significant increased risk for stroke and atherosclerosis. In addition to elevated blood pressure, hypertension is characterized by neuroendocrine and immune activation and cell adhesion molecule activation, including elevated levels of C-reactive protein (CRP), inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1) (CD54) and E-selectin (sCD62E), which are predictive of morbidity and mortality outcomes. Pharmacological treatment for hypertension successfully reduces blood pressure, but has limited effectiveness for reducing accompanying inflammation and its associated morbidity and mortality. Exercise and diet interventions have been shown to significantly reduce blood pressure, but few if any studies have examined effects on inflammation in hypertension or potential mechanisms. We will examine the effects of a 12-week exercise intervention and a 12-week exercise plus diet intervention on inflammation and cell adhesion in 150 patients with hypertension (blood pressure 140/90 mm Hg but 120/80 mm Hg but 140/90 mm Hg) who are currently not on anti-hypertensive medication. Prior to and following the interventions, we will assess resting and stress-induced (mental stressor and treadmill exercise testing) changes in circulating levels of CRP, IL-6, TNF-alpha, sICAM-1, sE-selectin, expression of the 2-integrin subunits CD11a and CD11b on leukocytes, leukocyte activation (pseudopod formation), and peripheral blood mononuclear cell (PBMC) chemotaxis. Hypothesis 1. Compared to a 12-week wait-list control group, the 12-week exercise intervention, and especially the 12-week exercise plus diet intervention, will reduce resting and stress-induced inflammation and cell adhesion. 1-1. Intervention groups will exhibit reduced levels of CRP, IL-6, TNF-alpha, sICAM-1, sE-selectin, leukocyte CD11a and CD11b expression, leukocyte activation, chemotaxis at rest pre to post intervention as compared to the wait list control group. 1-2. Intervention groups will exhibit reduced levels of CRP, IL-6, TNF-alpha, sICAM-1, sE-selectin, leukocyte CD11a and CD11b expression, leukocyte activation, and chemotaxis in response to the acute challenges pre to post intervention as compared to the wait list control group. Hypothesis 2. Compared to a 12-week wait-list control group, the 12-week exercise intervention, and especially the 12-week exercise plus diet intervention, will increase fitness levels, reduce urinary catecholamine and cortisol levels, and increase insulin sensitivity. [These hypothesized effects, while relatively straightforward and expected, need to be verified in order the test the mechanisms proposed in Hypothesis 3 below.] 2.1 Both exercise and exercise plus diet groups will show increased fitness levels as compared to the wait list control group. 2.2 Both exercise and exercise plus diet groups will show increased insulin sensitivity and decreased catecholamine and cortisol levels as compared to the wait list control group. 2.3 The exercise plus diet group will show greater weight reduction as compared to the exercise intervention or the wait list control group.