Kojda Georg, Hambrecht Rainer
Institut für Pharmakologie und Klinische Pharmakologie, Medizinische Einrichtungen, Heinrich-Heine-Universität, Moorenstr. 5, 40225 Düsseldorf, Germany.
Cardiovasc Res. 2005 Aug 1;67(2):187-97. doi: 10.1016/j.cardiores.2005.04.032.
A lack of exercise training and/or regular physical activity is a known risk factor for cardiovascular disease. Exercise training induces marked vascular remodeling by increasing angiogenesis and arteriogenesis. These changes in the architecture of the vascular tree are likely associated with functional changes and improved organ blood flow. Physical forces such as shear stress, transmural pressure and cyclic stretch activate mechanotransduction mechanisms in endothelial and smooth muscle cells that are mediated by integrins and associated RhoA small GTPase. They stimulate various signal transduction pathways involving phosphorylation of kinases such as focal adhesion kinase, c-Src, Akt kinase, phosphatidylinositol 3-kinase, myosin light chain kinase and mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinase (ERK). These mechanisms result in upregulation of genes mediating antiatherogenic effects by promoting antiapoptotic and antiproliferative signals, by increasing vascular NO bioavailability and by changing calcium handling and the vascular myogenic response to pressure. Exercise-induced increase of vascular eNOS expression and of eNOS Ser-1177 phosphorylation is most likely an important and potentially vasoprotective effect of exercise training. The underlying mechanisms involve cell membrane proteins such as integrins and products of vascular oxidative stress such as hydrogen peroxide. Exercise-induced eNOS expression is transient and reversible and regulated by factors such as angiogenesis, arteriogenesis and antioxidative effects including upregulation of superoxide dismutases (SOD1, SOD3) and downregulation of NAD(P)H oxidase, which likely blunts the effects of oxidative stress. Based on these observations, it appears reasonable to assume that exercise training can be viewed as an effective antioxidant and antiatherogenic therapy.
缺乏运动训练和/或规律的体育活动是已知的心血管疾病风险因素。运动训练通过增加血管生成和动脉生成诱导显著的血管重塑。血管树结构的这些变化可能与功能变化和器官血流改善有关。诸如剪切应力、跨壁压力和周期性拉伸等物理力激活内皮细胞和平滑肌细胞中的机械转导机制，这些机制由整合素和相关的RhoA小GTP酶介导。它们刺激各种信号转导途径，涉及激酶的磷酸化，如粘着斑激酶、c-Src、Akt激酶、磷脂酰肌醇3激酶、肌球蛋白轻链激酶和丝裂原活化蛋白激酶（MAPK），如细胞外信号调节激酶（ERK）。这些机制通过促进抗凋亡和抗增殖信号、增加血管一氧化氮生物利用度以及改变钙处理和血管对压力的肌源性反应，导致介导抗动脉粥样硬化作用的基因上调。运动诱导的血管内皮一氧化氮合酶（eNOS）表达增加和eNOS丝氨酸1177磷酸化很可能是运动训练的重要且潜在的血管保护作用。潜在机制涉及细胞膜蛋白如整合素和血管氧化应激产物如过氧化氢。运动诱导的eNOS表达是短暂且可逆的，并受血管生成、动脉生成和抗氧化作用等因素调节，包括超氧化物歧化酶（SOD1、SOD3）上调和NAD(P)H氧化酶下调，这可能减弱氧化应激的影响。基于这些观察结果，似乎有理由认为运动训练可被视为一种有效的抗氧化和抗动脉粥样硬化疗法。
