Iemitsu Motoyuki, Maeda Seiji, Jesmin Subrina, Otsuki Takeshi, Miyauchi Takashi
Institute of Health and Sport Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan.
Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1290-8. doi: 10.1152/ajpheart.00820.2005. Epub 2006 Apr 14.
Exercise training improves aging-induced deterioration of angiogenesis in the heart. However, the mechanisms underlying exercise-induced improvement of capillary density in the aged heart are unclear. Vascular endothelial growth factor (VEGF) is implicated in angiogenesis, which activated angiogenic signaling cascade through Akt and endothelial nitric oxide synthase (eNOS)-related pathway. We hypothesized that VEGF angiogenic signaling cascade in the heart contributes to a molecular mechanism of exercise training-induced improvement of capillary density in old age. With the use of hearts of sedentary young rats (4 mo old), sedentary aged rats (23 mo old), and exercise-trained aged rats (23 mo old, swim training for 8 wk), the present study investigated whether VEGF and VEGF-related angiogenic molecular expression in the aged heart is affected by exercise training. Total capillary density in the heart was significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas that in the exercise-trained rat was significantly higher than the sedentary aged rats. The mRNA and protein expressions of VEGF and of fms-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1), which are main VEGF receptors, in the heart were significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas those in the exercise-trained rats were significantly higher than those in the sedentary aged rats. The phosphorylation of Akt protein and eNOS protein in the heart corresponded to the changes in the VEGF protein levels. These findings suggest that exercise training improves aging-induced downregulation of cardiac VEGF angiogenic signaling cascade, thereby contributing to the exercise training-induced improvement of angiogenesis in old age.
运动训练可改善衰老引起的心脏血管生成恶化。然而，运动诱导老年心脏毛细血管密度改善的潜在机制尚不清楚。血管内皮生长因子（VEGF）与血管生成有关，它通过Akt和内皮型一氧化氮合酶（eNOS）相关途径激活血管生成信号级联反应。我们假设心脏中的VEGF血管生成信号级联反应有助于运动训练诱导老年毛细血管密度改善的分子机制。本研究使用久坐不动的年轻大鼠（4月龄）、久坐不动的老年大鼠（23月龄）和运动训练的老年大鼠（23月龄，游泳训练8周）的心脏，研究了运动训练是否会影响老年心脏中VEGF及VEGF相关血管生成分子的表达。与久坐不动的年轻大鼠相比，久坐不动的老年大鼠心脏中的总毛细血管密度显著降低，而运动训练大鼠的总毛细血管密度显著高于久坐不动的老年大鼠。与久坐不动的年轻大鼠相比，久坐不动的老年大鼠心脏中VEGF及其主要VEGF受体fms样酪氨酸激酶-1（Flt-1）和胎儿肝激酶-1（Flk-1）的mRNA和蛋白表达显著降低，而运动训练大鼠的这些表达显著高于久坐不动的老年大鼠。心脏中Akt蛋白和eNOS蛋白的磷酸化与VEGF蛋白水平的变化一致。这些发现表明，运动训练可改善衰老引起的心脏VEGF血管生成信号级联反应的下调，从而有助于运动训练诱导的老年血管生成改善。
