ABSTRACT
Objective: During aging, an ineffective perfusion of tissues/organs is a major risk factor for several diseases. Age-induced oxidative stress has been proposed to correlate with this age-related microvascular dysfunction including angiogenesis impairment. It has been demonstrated that exercise training could ameliorate oxidative damage, as well as, enhance angiogenesis in various organs. Therefore, the present study aims to investigate whether exercise training can prevent alterations of capillary vascularity in brain and bone during aging. Design and method: Male Wistar rats were divided into three groups: sedentary-young (aged 4-6 months), sedentary-aged (aged 20-22 months) and train-aged (aged 20-22 months). The exercise program included swimming training 5 days/week for 8 weeks. We directly observed microvasculature of brain and bone by using a laser scanning confocal microscopic system. The microvascular networks were visualized by fluorescein isothiocyanate labeled dextran and were analyzed for capillary vascularity by image analysis software. Blood was collected to determine the level of malondialdehyde, an indicator of oxidative stress. Results: In sedentary-aged group, the malondialdehyde level was significantly increased, whereas capillary vascularities in brain and bone were significantly decreased when compared to the sedentary-young group (P<0.05). In train-aged group, capillary vascularities in brain and bone were significantly higher, whereas the malondialdehyde level was significantly lower when compared to the sedentary-aged group (P<0.05). Besides, the result also showed a linear correlation between capillary vascularity and malondialdehyde level. Conclusion: The exercise training could attenuate age-induced suppression of capillary vascularity in brain and bone, closely related to exercise-ameliorated oxidative stress during aging.
ABSTRACT
Background: In a tumor, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) are induced to promote angiogenesis for the growth and metastasis of cells. There have been very few studies to examine in vivo relation between HIF-1α and VEGF during tumor progression. Objective: To study the relationship between HIF-1α and VEGF expressions under neovascularization induced by hepatocellular carcinoma cells (HepG2) implanted in nude mice. Methods: Male BALB/c-nude mice 8-10 weeks of age were used. A chamber was prepared on the dorsal skin in which HepG2 was transplanted to induce a tumor. On the day of the experiment, and on days 2, 7, and 14, microcirculation within the chamber was observed using fluorescence videomicroscopy. Based on the recorded video images, capillary vascularity (CV) was measured to examine tumor neovascularization. VEGF expression was measured in blood (serum) withdrawn, using enzyme immunoassay, while HIF-1α expression was measured on samples isolated from tumor tissue, using immunohistochemistry. Results: The measured CV significantly increased on day 7 and 14 compared to the aged-matched controls (p \< 0.05). HIF-1α markedly expressed on day 2, and the expression declined on day 7 and 14 post-inoculation. VEGF expression in serum increased more on day 7 and 14 than on day 2. HIF-1α expression decreased with the increase in VEGF expression from 2 to 14 days after HepG2 implantation, showing a reverse correlation. Conclusion: HIF-1α expression existed prior to both VEGF expression and neovascularization in the tumor. An inhibitor of HIF-1α might be a therapeutic agent for reducing neovascularization via adaptation to hypoxia in tumors.