Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization

Norihiro Nagai, Yuichi Oike, Kanako Izumi-Nagai, Takashi Urano, Yoshiaki Kubota, Kousuke Noda, Yoko Ozawa, Makoto Inoue, Kazuo Tsubota, Toshio Suda, Susumu Ishida

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

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-γ 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-γ-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.

Original languageEnglish
Pages (from-to)2252-2259
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number10
DOIs
Publication statusPublished - 2006 Oct 1

Keywords

  • Choroidal neovascularization
  • Inflammation
  • Intercellular adhesion molecule-1
  • Renin-angiotensin system
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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