Gu Jian-Wei, Gadonski Giovani, Wang Julie, Makey Ian, Adair Thomas H
Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
BMC Physiol. 2004 Jan 16;4:2. doi: 10.1186/1472-6793-4-2.
Physical inactivity increases the risk of atherosclerosis. However, the molecular mechanisms of this relation are poorly understood. A recent report indicates that endostatin, an endogenous angiostatic factor, inhibits the progression of atherosclerosis, and suggests that reducing intimal and atherosclerotic plaque tissue neovascularization can inhibit the progression atherosclerosis in animal models. We hypothesize that exercise can elevate the circulatory endostatin level. Hence, exercise can protect against one of the mechanisms of atherosclerosis.
We examined treadmill exercise tests in healthy volunteers to determine the effect of exercise on plasma levels of endostatin and other angiogenic regulators. Oxygen consumption (VO2) was calculated. Plasma levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined using ELISA. The total peak VO2 (L) in 7 male subjects was 29.5 +/- 17.8 over a 4-10 minute interval of exercise. Basal plasma levels of endostatin (immediately before exercise) were 20.3 +/- 3.2 pg/ml, the plasma levels increased to 29.3 +/- 4.2, 35.2 +/- 1.8, and 27.1 +/- 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a strong linear correlation between increased plasma levels of endostatin (%) and the total peak VO2 (L) related to exercise (R2 = 0.9388; P < 0.01). Concurrently, VEGF levels decreased to 28.3 +/- 6.4, 17.6 +/- 2.4, and 26.5 +/- 12.5 pg/ml, at 0.5, 2, and 6 h, respectively, after exercise. There were no significant changes in plasma bFGF levels in those subjects before and after exercise.
The results suggest that circulating endostatin can be significantly increased by exercise in proportion to the peak oxygen consumption under physiological conditions in healthy volunteers. These findings may provide new insights into the molecular links between physical inactivity and the risk of angiogenesis dependent diseases such as atherosclerosis.
缺乏体育活动会增加动脉粥样硬化的风险。然而，这种关系的分子机制尚不清楚。最近的一份报告表明，内皮抑素是一种内源性血管生成抑制因子，可抑制动脉粥样硬化的进展，并提示减少内膜和动脉粥样硬化斑块组织的新生血管形成可在动物模型中抑制动脉粥样硬化的进展。我们推测运动可以提高循环内皮抑素水平。因此，运动可以预防动脉粥样硬化的一种发病机制。
我们对健康志愿者进行了跑步机运动试验，以确定运动对血浆内皮抑素和其他血管生成调节因子水平的影响。计算了耗氧量（VO2）。使用酶联免疫吸附测定法测定血浆内皮抑素、血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的水平。7名男性受试者在4至10分钟的运动间隔内的总峰值VO2（L）为29.5±17.8。运动前（即基础状态）血浆内皮抑素水平为20.3±3.2 pg/ml，运动后0.5、2和6小时，血浆水平分别升至29.3±4.2、35.2±1.8和27.1±2.2 ng/ml。运动后血浆内皮抑素水平升高的百分比（%）与运动相关的总峰值VO2（L）之间存在很强的线性相关性（R2 = 0.9388；P < 0.01）。同时，运动后0.5、2和6小时，VEGF水平分别降至28.3±6.4、17.6±2.4和26.5±12.5 pg/ml。这些受试者运动前后血浆bFGF水平无显著变化。
结果表明，在健康志愿者的生理条件下，运动可使循环内皮抑素显著增加，且与峰值耗氧量成比例。这些发现可能为缺乏体育活动与诸如动脉粥样硬化等血管生成依赖性疾病风险之间的分子联系提供新的见解。
