| First Author | Ihara Y | Year | 2007 |
| Journal | J Mol Cell Cardiol | Volume | 43 |
| Issue | 4 | Pages | 455-64 |
| PubMed ID | 17761193 | Mgi Jnum | J:126372 |
| Mgi Id | MGI:3761082 | Doi | 10.1016/j.yjmcc.2007.07.044 |
| Citation | Ihara Y, et al. (2007) Upregulation of the ligand-RAGE pathway via the angiotensin II type I receptor is essential in the pathogenesis of diabetic atherosclerosis. J Mol Cell Cardiol 43(4):455-64 |
| abstractText | The receptor for advanced glycation end products (RAGE) and the angiotensin II type I receptor (AT1R) have been separately linked to the pathogenesis of diabetic atherosclerosis. However, no prior study has addressed a linkage between RAGE and AT1R in diabetic atherogenesis. Therefore, we tested the hypothesis that upregulation of the ligand-RAGE axis via AT1R is an essential process underlying the disease. Diabetes was induced in apolipoprotein E-deficient (ApoE(-/-)) mice by streptozotocin, and diabetic mice were treated with AT1 receptor blocker (ARB) for 6 weeks. Diabetic ApoE(-/-) mice that were AT1R-deficient (ApoE(-/-)AT1aR(-/-)) were also investigated. In diabetic ApoE(-/-) mice, AT1R was found to increase within 1 week of diabetes induction, before ligand-RAGE pathway activation and other inflammatory changes were observed. Both ARB treatment and AT1aR deficiency suppressed diabetic atherosclerosis, ligand-RAGE expression and inflammatory changes. In contrast, upregulation of the ligand-RAGE pathway was noted in atherosclerotic plaques from non-diabetic ApoE(-/-) mice infused with angiotensin II. In cultured vascular smooth muscle cells, angiotensin II increased RAGE protein levels via AT1R stimulation. Upregulation of the ligand-RAGE pathway via AT1R is an essential mechanism in diabetic atherosclerosis, implying that ARB might decrease diabetic atherogenesis by inhibiting ligand-RAGE signals. |
