| First Author | Imanishi M | Year | 2014 |
| Journal | Cardiovasc Res | Volume | 102 |
| Issue | 3 | Pages | 460-8 |
| PubMed ID | 24623277 | Mgi Jnum | J:229584 |
| Mgi Id | MGI:5752465 | Doi | 10.1093/cvr/cvu061 |
| Citation | Imanishi M, et al. (2014) Smooth muscle cell-specific Hif-1alpha deficiency suppresses angiotensin II-induced vascular remodelling in mice. Cardiovasc Res 102(3):460-8 |
| abstractText | AIM: Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1alpha (Hif-1alpha) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. METHODS AND RESULTS: To clarify the role of Hif-1alpha in vascular remodelling, we created mice lacking the Hif-1alpha gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1alpha up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1alpha suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1alpha deficiency. In addition, the SMC-specific Hif-1alpha deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1alpha functions as an intrinsic modulator of vascular remodelling-related gene expression. CONCLUSION: Our results revealed that SMC-derived Hif-1alpha is a crucial mediator of Ang II-induced vascular remodelling. |
