Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease.
Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease.
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DOI：
10.1097/00008483-199911000-00018
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发表时间：
1999-05
期刊：
影响因子：
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通讯作者：
J. Smith;R. Dykes;J. E. Douglas;G. Krishnaswamy;S. Berk
中科院分区：
文献类型：
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作者：
J. Smith;R. Dykes;J. E. Douglas;G. Krishnaswamy;S. Berk
越来越多的证据表明，动脉粥样硬化是一种免疫介导的疾病，其中通过浸润血液单核细胞分泌致动脉粥样硬化和动脉粥样硬化保护细胞因子起着重要作用。目前尚不清楚长期运动是否会直接改变这种致动脉粥样硬化和抗动脉粥样硬化的活性。目的确定长期运动对缺血性心脏病高危人群血液单核细胞致动脉粥样硬化活性的影响。设计前后试验，采用6个月的个性化，监督运动计划，从1996年12月至1997年10月的招募期。设置医院为基础的社区健康中心。参与者在110名响应公众志愿者请求的人中，52人符合纳入标准（基于血清补体和/或C反应蛋白水平的心肌梗死风险比≥ 1.7，以及正常的运动平板试验结果）。52名入组者中的43名（25名女性[平均年龄，49.7岁]和18名男性[平均年龄，48.1岁]）完成了研究; 9名因个人原因退出。缺血性心脏病的其他风险因素包括高胆固醇血症（65.1%）、冠心病家族史（62.8%）、不活动（60.5%）、高血压（32.6%）、肥胖（25.6%）、吸烟（11.6%）和糖尿病（4.7%）。主要观察指标：比较基线和运动计划完成后的血液水平，包括自发和植物血凝素诱导的白细胞介素1 α、肿瘤坏死因子α和干扰素γ的产生（致动脉粥样硬化细胞因子）和白细胞介素4、白细胞介素10和转化生长因子β 1（动脉粥样硬化保护性细胞因子）;淋巴细胞表型和对植物血凝素的促有丝分裂反应;和血清C-反应蛋白水平。结果受试者每周平均锻炼2.5（范围，0.3-7.4）小时。运动后单核细胞产生的致动脉粥样硬化细胞因子下降了58.3%（P<0.001），而产生的动脉粥样硬化保护细胞因子上升了35.9%（P<0.001）。运动后转化生长因子β 1和植物血凝素诱导的致动脉粥样硬化细胞因子产生的变化与受试者进行重复性下半身运动运动的时间成比例（P<0.02），表明存在剂量反应关系。运动后，细胞功能的变化全身反映在血清C-反应蛋白水平下降35%（P= 0.12）。结论：我们的数据表明，长期运动可降低缺血性心脏病患者血液单核细胞的致动脉粥样硬化活性。这可能是身体活动预防缺血性心脏病的一种机制。
CONTEXT Increasing evidence demonstrates that atherosclerosis is an immunologically mediated disease in which the secretion of atherogenic and atheroprotective cytokines, by infiltrating blood mononuclear cells, plays an important role. It is not known whether long-term exercise alters this atherogenic and atheroprotective activity directly. OBJECTIVE To determine the effect of long-term exercise on the atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. DESIGN Before-after trial using a 6-month individualized, supervised exercise program, with an enrollment period from December 1996 to October 1997. SETTING Hospital-based community wellness center. PARTICIPANTS Of 110 persons who responded to a public request for volunteers, 52 met the inclusion criteria (risk ratio for myocardial infarction > or =1.7 based on serum complement and/or C-reactive protein levels, and normal exercise treadmill test results). Forty-three of the 52 enrollees (25 women [mean age, 49.7 years] and 18 men [mean age, 48.1 years]) completed the study; 9 withdrew for personal reasons. Additional risk factors for ischemic heart disease included hypercholesterolemia (65.1 %), a family history of coronary heart disease (62.8%), inactivity (60.5%), hypertension (32.6%), obesity (25.6%), smoking (11.6%), and diabetes mellitus (4.7%). MAIN OUTCOME MEASURES Blood levels were compared at baseline and after the exercise program had been completed for the following: spontaneous and phytohemagglutinin-induced production of interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma (atherogenic cytokines), and interleukin 4, interleukin 10, and transforming growth factor beta 1 (atheroprotective cytokines) by blood mononuclear cells; lymphocyte phenotypes and mitogenic responses to phytohemagglutinin; and serum C-reactive protein levels. RESULTS Subjects exercised for a mean of 2.5 (range, 0.3-7.4) hours per week. Mononuclear cell production of atherogenic cytokines fell by 58.3 % (P<.001) following the exercise program, where as the production of atheroprotective cytokines rose by 35.9% (P<.001). Changes in transforming growth factor beta 1 and in phytohemagglutinin-induced atherogenic cytokine production after the exercise program were proportionate to the time subjects spent performing repetitive lower-body motion exercises (P<.02), indicating a dose-response relationship. After the exercise program, changes in cellular function were reflected systemically by a 35% decrease in serum levels of C-reactive protein (P=.12). CONCLUSIONS Our data suggest that long-term exercise decreases the atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. This may be a mechanism whereby physical activity protects against ischemic heart disease.