Effects of Aging and Hypoxia-Inducible Factor-1 Activity on Angiogenic Cell Mobilization and Recovery of Perfusion After Limb Ischemia
| العنوان: | Effects of Aging and Hypoxia-Inducible Factor-1 Activity on Angiogenic Cell Mobilization and Recovery of Perfusion After Limb Ischemia |
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| المؤلفون: | Yi Fu Zhou, Marta Bosch-Marce, Lindsey Savino, Alireza Rabi, Robert S. Kerbel, Yuval Shaked, Marianne Strazza, Youn Na, Huafeng Zhang, Sergio Rey, Theresa LaVallee, Kakali Sarkar, Gregg L. Semenza, Hiroaki Okuyama, Jacob B. Wesley, Hideo Kimura, Ye V. Liu, Scott Vandiver, Karin R. McDonald |
| المصدر: | Circulation Research. 101:1310-1318 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Senescence, Aging, medicine.medical_specialty, Physiology, Angiogenesis, Genetic enhancement, Cell, Ischemia, Mice, Transgenic, Stem cell factor, Mice, Cell Movement, Limb perfusion, Animals, Medicine, Cells, Cultured, Mice, Knockout, Neovascularization, Pathologic, business.industry, Hypoxia (medical), medicine.disease, Surgery, medicine.anatomical_structure, Lower Extremity, Reperfusion, Cancer research, Hypoxia-Inducible Factor 1, medicine.symptom, Cardiology and Cardiovascular Medicine, business |
| الوصف: | 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-1α, 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-1α gene therapy can counteract the pathological effects of aging in a mouse model of limb ischemia. |
| تدمد: | 1524-4571 0009-7330 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b74e0b8aba68d6a63b7ffb25ea6aa060Test https://doi.org/10.1161/circresaha.107.153346Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b74e0b8aba68d6a63b7ffb25ea6aa060 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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