| First Author | Xu MJ | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 8 | Pages | 1757-65 |
| PubMed ID | 21597006 | Mgi Jnum | J:191859 |
| Mgi Id | MGI:5463203 | Doi | 10.1161/ATVBAHA.111.227991 |
| Citation | Xu MJ, et al. (2011) Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits. Arterioscler Thromb Vasc Biol 31(8):1757-65 |
| abstractText | OBJECTIVE: The aim of the present study was to determine whether mitochondrial uncoupling protein (UCP) 2 is required for AMPK-dependent angiogenesis in ischemia in vivo. METHODS AND RESULTS: Angiogenesis was assayed by monitoring endothelial tube formation (a surrogate for angiogenesis) in human umbilical vein endothelial cells (ECs), isolated mouse aortic endothelial cells (MAECs), and pulmonary microvascular endothelial cells or in ischemic thigh adductor muscles from wild-type (WT) mice or mice deficient in either AMPKalpha1 or AMPKalpha2. AMPK inhibition with pharmacological inhibitor (compound C) or genetic means (transfection of AMPKalpha-specific small interfering RNA) significantly lowered the tube formation in human umbilical vein ECs. Consistently, compared with WT mice, tube formation in MAECs isolated from either AMPKalpha1(-/-) or AMPKalpha2(-/-) mice, which exhibited oxidative stress and reduced expression of UCP2, was significantly impaired. In addition, adenoviral overexpression of UCP2, but not adenoviruses encoding green fluorescent protein, normalized tube formation in MAECs from either AMPKalpha1(-/-) or AMPKalpha2(-/-) mice. Similarly, supplementation with sodium nitroprusside, a nitric oxide (NO) donor, restored tube formation. Furthermore, ischemia significantly increased angiogenesis, serine 1177 phosphorylation of endothelial NO synthase, and UCP2 in ischemic thigh adductor muscles from WT mice but not in those from either AMPKalpha1(-/-) or AMPKalpha2(-/-) mice. CONCLUSIONS: We conclude that AMPK-dependent UCP2 expression in ECs promotes angiogenesis in vivo. |
