Effect of aging on collateral vessel growth in rats with ischemic hind limbs.

BACKGROUND: Animal experiments have found that injection of angiogenic cells or growth factors into experimental animals significantly promotes the growth of collateral vessels. However, a large number of clinical randomized controlled trials, including administration of angiogenic cells to patients with severe lower limb ischemia or myocardial infarction, have been ineffective to restore the blood flow in ischemic tissues. By comparing the remarkable effects of animal experiments and disappointing clinical trial results, it may reflect a fact that young animals are used in most laboratories, while most of the patients with ischemic diseases are elderly. OBJECTIVE: To explore the effect of aging on the growth of collateral vessels in ischemic hind limbs in adult and aged rat models of femoral artery ligation. METHODS: Twelve healthy adult rats (6-month-old) were divided into adult sham group and adult ligation group, and 12 aged rats (20-month-old) were divided into aged sham group and aged ligation group. Rats in the ligation groups underwent femoral artery ligation. The rats survived for 1 week after surgery. Three rats in each group were taken and the muscles with collateral vessels in the hind limbs were taken for frozen section for immunofluorescence histochemical detection of endothelial nitric oxide synthase, Ki67 and matrix metalloproteinase 2. Another three rats from each group were subjected to angiography using gelatin trioxide and X-ray for observing the growth of collateral vessels. RESULTS AND CONCLUSION: Compared with the sham groups, rats in the ligation groups had more collateral vessels in hind limbs, increased number of Ki67-positive cells and increased expression of endothelial nitric oxide synthase and matrix metalloproteinase 2 (P < 0.01). Compared with the adult ligation group, the number of collateral vessels was less (P < 0.01), the number of Ki67 positive cells was reduced (P < 0.01), and the expression of endothelial nitric oxide synthase and matrix metalloproteinase 2 was significantly decreased in the aged ligation group (P < 0.01). Overall, aging impairs the growth of collateral vessels in ischemic hind limbs of rats. [ABSTRACT FROM AUTHOR]