| First Author | Kubota R | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 402 |
| Issue | 2 | Pages | 396-401 |
| PubMed ID | 20946870 | Mgi Jnum | J:166460 |
| Mgi Id | MGI:4845804 | Doi | 10.1016/j.bbrc.2010.10.043 |
| Citation | Kubota R, et al. (2010) Ischemia-induced angiogenesis is impaired in aminopeptidase A deficient mice via down-regulation of HIF-1alpha. Biochem Biophys Res Commun 402(2):396-401 |
| abstractText | Aminopeptidase A (APA; EC 3.4.11.7) is a transmembrane metalloprotease with several functions in tumor angiogenesis. To investigate the role of APA in the process of ischemia-induced angiogenesis, we evaluated the cellular angiogenic responses under hypoxic conditions and the process of perfusion recovery in the hindlimb ischemia model of APA-deficient (APA-KO; C57Bl6/J strain) mice. Western blotting of endothelial cells (ECs) isolated from the aorta of APA-KO mice revealed that the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein in response to hypoxic challenge was blunted. Regarding the proteasomal ubiquitination, a proteasome inhibitor MG-132 restored the reduced accumulation of HIF-1alpha in ECs from APA-KO mice similar to control mice under hypoxic conditions. These were associated with decreased growth factor secretion and capillary formation in APA-KO mice. In the hindlimb ischemia model, perfusion recovery in APA-KO mice was decreased in accordance with a significantly lower capillary density at 2weeks. Regarding vasculogenesis, no differences were observed in cell populations and distribution patterns between wild type and APA-KO mice in relation to endothelial progenitor cells. Our results suggested that Ischemia-induced angiogenesis is impaired in APA-KO mice partly through decreased HIF-1alpha stability by proteasomal degradation and subsequent suppression of HIF-1alpha-driven target protein expression such as growth factors. APA is a functional target for ischemia-induced angiogenesis. |
