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Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF.
Cell Tissue Res. 2005 Jun; 320(3):437-45.CT

Abstract

Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system, regulates numerous inflammatory-proliferative responses in vascular wall cells and is thus involved in atherosclerosis. We have previously shown that pigment epithelium-derived factor (PEDF) inhibits advanced glycation end-product-induced pericyte apoptosis, thereby exerting beneficial effects on diabetic retinopathy. However, a role for PEDF in vascular inflammation and atherosclerosis remains to be elucidated. In this study, we have examined whether PEDF inhibits the Ang-II-induced endothelial cell (EC) activation in vitro and the way that it might achieve this effect. Ang II significantly induced redox-sensitive transcriptional factor NF-kappaB activation and subsequent monocyte chemoattractant protein-1 expression in human umbilical vein ECs (HUVEC), both of which were completely inhibited by PEDF or the anti-oxidant N-acetylcysteine. PEDF or diphenylene iodonium, an inhibitor of NADPH oxidase, inhibited Ang-II-induced intracellular reactive oxygen species (ROS) generation in HUVEC. Furthermore, PEDF inhibited Ang-II-induced up-regulation of mRNA levels of p22phox, Nox4, and gp91phox/Nox2, which are membrane components of NADPH oxidase, and its enzymatic activity in HUVEC. Antisense, but not sense, DNAs against p22phox, Nox4, or gp91phox/Nox2 were found significantly to inhibit Ang-II-induced ROS generation in HUVEC. These results demonstrate that PEDF inhibits Ang-II-induced EC activation by suppressing NADPH-oxidase-mediated ROS generation and that PEDF may play a protective role in the development and progression of atherosclerosis.

Authors+Show Affiliations

Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. shoichi@med.kurume-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15846509

Citation

Yamagishi, Sho-Ichi, et al. "Pigment Epithelium-derived Factor (PEDF) Blocks Angiotensin II Signaling in Endothelial Cells Via Suppression of NADPH Oxidase: a Novel Anti-oxidative Mechanism of PEDF." Cell and Tissue Research, vol. 320, no. 3, 2005, pp. 437-45.
Yamagishi S, Nakamura K, Ueda S, et al. Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF. Cell Tissue Res. 2005;320(3):437-45.
Yamagishi, S., Nakamura, K., Ueda, S., Kato, S., & Imaizumi, T. (2005). Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF. Cell and Tissue Research, 320(3), 437-45.
Yamagishi S, et al. Pigment Epithelium-derived Factor (PEDF) Blocks Angiotensin II Signaling in Endothelial Cells Via Suppression of NADPH Oxidase: a Novel Anti-oxidative Mechanism of PEDF. Cell Tissue Res. 2005;320(3):437-45. PubMed PMID: 15846509.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF. AU - Yamagishi,Sho-Ichi, AU - Nakamura,Kazuo, AU - Ueda,Seiji, AU - Kato,Seiya, AU - Imaizumi,Tsutomu, Y1 - 2005/04/22/ PY - 2004/11/08/received PY - 2005/02/08/accepted PY - 2005/4/23/pubmed PY - 2006/2/1/medline PY - 2005/4/23/entrez SP - 437 EP - 45 JF - Cell and tissue research JO - Cell Tissue Res VL - 320 IS - 3 N2 - Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system, regulates numerous inflammatory-proliferative responses in vascular wall cells and is thus involved in atherosclerosis. We have previously shown that pigment epithelium-derived factor (PEDF) inhibits advanced glycation end-product-induced pericyte apoptosis, thereby exerting beneficial effects on diabetic retinopathy. However, a role for PEDF in vascular inflammation and atherosclerosis remains to be elucidated. In this study, we have examined whether PEDF inhibits the Ang-II-induced endothelial cell (EC) activation in vitro and the way that it might achieve this effect. Ang II significantly induced redox-sensitive transcriptional factor NF-kappaB activation and subsequent monocyte chemoattractant protein-1 expression in human umbilical vein ECs (HUVEC), both of which were completely inhibited by PEDF or the anti-oxidant N-acetylcysteine. PEDF or diphenylene iodonium, an inhibitor of NADPH oxidase, inhibited Ang-II-induced intracellular reactive oxygen species (ROS) generation in HUVEC. Furthermore, PEDF inhibited Ang-II-induced up-regulation of mRNA levels of p22phox, Nox4, and gp91phox/Nox2, which are membrane components of NADPH oxidase, and its enzymatic activity in HUVEC. Antisense, but not sense, DNAs against p22phox, Nox4, or gp91phox/Nox2 were found significantly to inhibit Ang-II-induced ROS generation in HUVEC. These results demonstrate that PEDF inhibits Ang-II-induced EC activation by suppressing NADPH-oxidase-mediated ROS generation and that PEDF may play a protective role in the development and progression of atherosclerosis. SN - 0302-766X UR - https://www.unboundmedicine.com/medline/citation/15846509/Pigment_epithelium_derived_factor__PEDF__blocks_angiotensin_II_signaling_in_endothelial_cells_via_suppression_of_NADPH_oxidase:_a_novel_anti_oxidative_mechanism_of_PEDF_ L2 - https://dx.doi.org/10.1007/s00441-005-1094-8 DB - PRIME DP - Unbound Medicine ER -