| First Author | Nagai N | Year | 2006 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 26 |
| Issue | 10 | Pages | 2252-9 |
| PubMed ID | 16888236 | Mgi Jnum | J:128066 |
| Mgi Id | MGI:3765421 | Doi | 10.1161/01.ATV.0000240050.15321.fe |
| Citation | Nagai N, et al. (2006) Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization. Arterioscler Thromb Vasc Biol 26(10):2252-9 |
| abstractText | BACKGROUND: Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration, the most common cause of blindness in the developed countries. The aim of the current study was to determine the involvement of the renin-angiotensin system (RAS) with the development of CNV, using human surgical samples and the murine model of laser-induced CNV. METHODS AND RESULTS: In the human and murine CNV tissues, the vascular endothelium expressed angiotensin II type 1 receptor (AT1-R), AT2-R, and angiotensin II. The CNV volume was significantly suppressed by treatment with an AT1-R blocker telmisartan, but not with an AT2-R blocker. AT1-R signaling blockade with telmisartan inhibited various inflammatory mechanisms including macrophage infiltration and upregulation of VEGF, intercellular adhesion molecule-1 (ICAM-1), MCP-1, and IL-6 in the retinal pigment epithelium-choroid complex. A PPAR-gamma antagonist partially but significantly reversed the suppressive effect of telmisartan on in vivo induction of CNV and in vitro upregulation of ICAM-1 and MCP-1 in endothelial cells and IL-6 in macrophages, showing the dual contribution of PPAR-gamma-agonistic and AT1-R-antagonistic actions in the telmisartan treatment. CONCLUSIONS: AT1-R-mediated inflammation plays a pivotal role in the development of CNV, indicating the possibility of AT1-R blockade as a novel therapeutic strategy to inhibit CNV. |
