Short communication: PPARγ mediates a direct antiangiogenic effect of ω3-PUFAs in proliferative retinopathy

Andreas Stahl; Przemyslaw Sapieha; Kip M. Connor; John Paul Sangiovanni; Jing Chen; Christopher M. Aderman; Keirnan L. Willett; Nathan M. Krah; Roberta J. Dennison; Molly R. Seaward; Karen I. Guerin; Jing Hua; Lois E.H. Smith

doi:10.1161/CIRCRESAHA.110.221317

Short communication: PPARγ mediates a direct antiangiogenic effect of ω3-PUFAs in proliferative retinopathy

Andreas Stahl, Przemyslaw Sapieha, Kip M. Connor, John Paul Sangiovanni, Jing Chen, Christopher M. Aderman, Keirnan L. Willett, Nathan M. Krah, Roberta J. Dennison, Molly R. Seaward, Karen I. Guerin, Jing Hua, Lois E.H. Smith

Research output: Contribution to journal › Article › peer-review

91 Scopus citations

Abstract

Rationale: Omega3 long-chain polyunsaturated fatty acids (ω3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing ω3-PUFA-dependent attenuation of angiogenesis. Objective: This study aims to identify a major mechanism by which ω3-PUFAs attenuate retinal neovascularization. Methods and Results: Administering ω3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)γ almost completely abrogates this effect. Inhibition of PPARγ also reverses the ω3-PUFA-induced reduction of retinal tumor necrosis factor-α, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor. Conclusions: These results identify a direct, PPARγ-mediated effect of ω3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.

Original language	English (US)
Pages (from-to)	495-500
Number of pages	6
Journal	Circulation research
Volume	107
Issue number	4
DOIs	https://doi.org/10.1161/CIRCRESAHA.110.221317
State	Published - Aug 20 2010
Externally published	Yes

Keywords

PPAR
neovascularization
omega 3 PUFA
oxygen-induced retinopathy
retinopathy

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine

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10.1161/CIRCRESAHA.110.221317

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Stahl, A., Sapieha, P., Connor, K. M., Sangiovanni, J. P., Chen, J., Aderman, C. M., Willett, K. L., Krah, N. M., Dennison, R. J., Seaward, M. R., Guerin, K. I., Hua, J., & Smith, L. E. H. (2010). Short communication: PPARγ mediates a direct antiangiogenic effect of ω3-PUFAs in proliferative retinopathy. Circulation research, 107(4), 495-500. https://doi.org/10.1161/CIRCRESAHA.110.221317

Stahl, A, Sapieha, P, Connor, KM, Sangiovanni, JP, Chen, J, Aderman, CM, Willett, KL, Krah, NM, Dennison, RJ, Seaward, MR, Guerin, KI, Hua, J & Smith, LEH 2010, 'Short communication: PPARγ mediates a direct antiangiogenic effect of ω3-PUFAs in proliferative retinopathy', Circulation research, vol. 107, no. 4, pp. 495-500. https://doi.org/10.1161/CIRCRESAHA.110.221317

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abstract = "Rationale: Omega3 long-chain polyunsaturated fatty acids (ω3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing ω3-PUFA-dependent attenuation of angiogenesis. Objective: This study aims to identify a major mechanism by which ω3-PUFAs attenuate retinal neovascularization. Methods and Results: Administering ω3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)γ almost completely abrogates this effect. Inhibition of PPARγ also reverses the ω3-PUFA-induced reduction of retinal tumor necrosis factor-α, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor. Conclusions: These results identify a direct, PPARγ-mediated effect of ω3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.",

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author = "Andreas Stahl and Przemyslaw Sapieha and Connor, {Kip M.} and Sangiovanni, {John Paul} and Jing Chen and Aderman, {Christopher M.} and Willett, {Keirnan L.} and Krah, {Nathan M.} and Dennison, {Roberta J.} and Seaward, {Molly R.} and Guerin, {Karen I.} and Jing Hua and Smith, {Lois E.H.}",

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AU - Sapieha, Przemyslaw

AU - Connor, Kip M.

AU - Sangiovanni, John Paul

AU - Chen, Jing

AU - Aderman, Christopher M.

AU - Willett, Keirnan L.

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AU - Dennison, Roberta J.

AU - Seaward, Molly R.

AU - Guerin, Karen I.

AU - Hua, Jing

AU - Smith, Lois E.H.

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AB - Rationale: Omega3 long-chain polyunsaturated fatty acids (ω3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing ω3-PUFA-dependent attenuation of angiogenesis. Objective: This study aims to identify a major mechanism by which ω3-PUFAs attenuate retinal neovascularization. Methods and Results: Administering ω3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)γ almost completely abrogates this effect. Inhibition of PPARγ also reverses the ω3-PUFA-induced reduction of retinal tumor necrosis factor-α, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor. Conclusions: These results identify a direct, PPARγ-mediated effect of ω3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.

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Short communication: PPARγ mediates a direct antiangiogenic effect of ω3-PUFAs in proliferative retinopathy

Abstract

Keywords

ASJC Scopus subject areas

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