Published online before print April 2, 2009, doi: 10.1161/CIRCRESAHA.109.194506
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© 2009 American Heart Association, Inc.
Molecular Medicine |
Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor-
Expression
From Molecular Cardiology/Whitaker Cardiovascular Institute (A.H., K.O., K.W., N.O.), Boston University School of Medicine, Mass; and Department of Metabolic Medicine (S.K.), Graduate School of Medicine, Osaka University, Japan.
Correspondence to Noriyuki Ouchi, MD, PhD, Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St, W611, Boston, MA 02118. E-mail nouchi{at}bu.edu
The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypoxia. When neonatal mice were subjected to ischemia-induced retinopathy, pathological retinal neovascularization during ischemia was exacerbated in adiponectin-knockout (APN-KO) mice compared with wild-type mice (neovascular area: 17.0±1.0% versus 11.7±0.6%, respectively). APN-KO mice also exhibited increased leukocyte adhesion (2.3±0.4-fold) and tumor necrosis factor (TNF)-
expression (2.6±0.2-fold) in hypoxic retina. Adenovirus-mediated overexpression of adiponectin attenuated hypoxia-induced pathological retinal neovascularization by 35% in wild-type mice and by 40% in APN-KO mice and leukostasis by 64% in wild-type mice and by 75% in APN-KO mice, which were associated with reduced TNF- production. TNF- blockade diminished the enhanced pathological neovascularization in APN-KO mice by 34%, and the inhibitory effects of adiponectin overexpression on retinal neovascularization and leukocyte adhesion were abolished in mice lacking TNF-. These data provide evidence that adiponectin protects against retinal vessel injury following pathological stimuli through modulation of TNF- inflammatory responses.
Key Words: adiponectin • neovascularization • ischemia • inflammation • angiogenesis
Related Article:
Circ. Res. 2009 104: 1029-1031.
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