June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Hypertension-induced Ang II promotes tube formation via MCP-1/MCPIP induction
Author Affiliations & Notes
  • Maria Marin Castano
    Ophthalmology, University of Miami, Miami, FL
  • Wen-Hsiang Lee
    Ophthalmology, University of Miami, Miami, FL
  • Eleut Hernandez
    Ophthalmology, University of Miami, Miami, FL
  • Francoise Praddaude
    Physiology and Pharmacology, University Paul Sabatier/INSERM-U 338, Toulouse, France
  • Christiane Pecher
    Physiology and Pharmacology, University Paul Sabatier/INSERM-U 338, Toulouse, France
  • Scott Cousins
    Ophthalmology, Duke University Eye Center, Durham, NC
  • Footnotes
    Commercial Relationships Maria Marin Castano, None; Wen-Hsiang Lee, None; Eleut Hernandez, None; Francoise Praddaude, None; Christiane Pecher, None; Scott Cousins, Alcon (F), Alcon (C), Heidelberg Engineering (C), Narrow River (C), Nordic Biotech (C), PanOptica (C), Pfizer (C), Salutaris Medical Devices (C), Sanofi-Fovea (C), Valeant Ophthalmics (C), Imagen Biotech (I)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6089. doi:
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      Maria Marin Castano, Wen-Hsiang Lee, Eleut Hernandez, Francoise Praddaude, Christiane Pecher, Scott Cousins; Hypertension-induced Ang II promotes tube formation via MCP-1/MCPIP induction. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6089.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: A number of systemic risk factors have been revealed as determinants for developing AMD. The renin-angiotensin system is of particular interest among these factors, due to the increasing incidence of hypertension (HTN) in Western societies. HTN was associated with the development of wet AMD. However, the mechanism(s) by which HTN may induce or contribute to CNV remains to be explored. Inflammation is a key cellular process with a central role in AMD and aberrant expression of chemokines occurs in diseases that have an inflammatory component. Retinal pigment epithelium (RPE) cells secret several of these chemokines including MCP-1, which has been proposed to be implicated in angiogenesis. HTN-associated hormone angiotensin II (Ang-II), is known to induce angiogenesis by stimulating expression of MCP-1. Moreover, it has been demonstrated that MCP-1 promotes angiogenesis via the novel protein MCPIP (MCP-1 induced protein). We previously demonstrated that Ang-II upregulates MCP-1 expression via AT1 receptor interaction in human RPE cells. Therefore, we postulate that Ang-II, through interactions with its receptor AT1, will induce expression of MCP-1 and MCPIP, which will promote tube formation in choroidal microvascular endothelial (cEC) cells contributing to CNV.

Methods: Mice were infused via osmotic minipumps for 4 weeks with saline (a), Ang II (b), and Ang II in combination with candesartan (c). Blood pressure was recorded before and after treatment. At the end of the experimental period, animals were sacrificed and eyes removed for recovery of RPE sheets. MCP-1 and MCPIP expression was analyzed by real-time PCR and Western blot. In parallel experiments; a) confluent ARPE-19 cells were exposed to Ang II (10-7M) with or without candesartan (10-7M), or to 50 pg/ml MCP-1 for 24 hours and b) cEC were treated with conditioned medium isolated from RPE exposed to Ang II and/or MCP-1 for 24 hours. MCP-1 and MCPIP mRNA and protein expression were analyzed as mentioned above. MCP-1 secretion was analyzed by ELISA and cell tube determined.

Results: Ang II increased MCP-1 and MCPIP expression in mouse RPE sheets thought AT1 receptor. Also, MCP-1 induced expression of MCPIP by RPE cells, which led to tube formation in cEC.

Conclusions: Our data support the hypothesis that Ang II, through MCP-1/MCPIP, may contribute to CNV, suggesting a pathogenic mechanism to explain the link between HTN and CNV.

Keywords: 412 age-related macular degeneration • 701 retinal pigment epithelium • 557 inflammation  

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