RESUMO
Ischemia is a stimulus for production of angiogenic cytokines that activate local vascular cells and mobilize angiogenic cells to the circulation. These responses are impaired in elderly patients with peripheral arterial disease. Hypoxia-inducible factor (HIF)-1 mediates adaptive responses to ischemia, including production of angiogenic cytokines. In this study, we demonstrate that aging and HIF-1 loss-of-function impair the expression of multiple angiogenic cytokines, mobilization of angiogenic cells, maintenance of tissue viability, and recovery of limb perfusion following femoral artery ligation. We show that HIF-1 directly activates transcription of the gene encoding stem cell factor and that mice lacking the cognate receptor C-KIT have impaired recovery from ischemia. Administration of AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, improved the recovery of perfusion in older mice to levels similar to those in young mice. Injection of AdCA5 into nonischemic limb was sufficient to increase the number of circulating angiogenic cells. These results indicate that HIF-1 activity is necessary and sufficient for the mobilization of angiogenic cells and that HIF-1alpha gene therapy can counteract the pathological effects of aging in a mouse model of limb ischemia.
Assuntos
Envelhecimento/metabolismo , Movimento Celular/fisiologia , Fator 1 Induzível por Hipóxia/metabolismo , Isquemia/genética , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Neovascularização Patológica/genética , Neovascularização Patológica/terapia , Envelhecimento/genética , Envelhecimento/patologia , Animais , Movimento Celular/genética , Células Cultivadas , Fator 1 Induzível por Hipóxia/genética , Fator 1 Induzível por Hipóxia/uso terapêutico , Isquemia/metabolismo , Isquemia/patologia , Extremidade Inferior/fisiologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Neovascularização Patológica/metabolismo , Reperfusão/métodosRESUMO
BACKGROUND: Anecdotal and experimental evidence suggest that a sitting position with maximum knee extension, hip adduction, and forward lean (hamstring stretch position) may produce better reversal of the lumbar lordosis than a traditional sitting position. METHODS: In a randomized trial during initiation of epidural labor analgesia, we compared the traditional versus hamstring stretch positions. The primary outcome was the number of needle-bone contacts. RESULTS: The groups were equivalent with respect to the number of needle-bone contacts. CONCLUSIONS: The hamstring stretch position is equivalent to the traditional sitting position in terms of the number of needle-bone contacts encountered when placing labor epidural needles.