Cargando…

Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS

We investigated the effect of peroxisome proliferator-activated receptor δ (PPARδ) on angiotensin II (Ang II)-triggered hypertrophy of vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand of PPARδ, significantly inhibited Ang II-stimulated protein synthesis in a c...

Descripción completa

Detalles Bibliográficos
Autores principales: Kang, Eun Sil, Hwang, Jung Seok, Lee, Won Jin, Lee, Gyeong Hee, Choi, Mi-Jung, Paek, Kyung Shin, Lim, Dae-Seog, Seo, Han Geuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324793/
https://www.ncbi.nlm.nih.gov/pubmed/30620754
http://dx.doi.org/10.1371/journal.pone.0210482
_version_ 1783386031085584384
author Kang, Eun Sil
Hwang, Jung Seok
Lee, Won Jin
Lee, Gyeong Hee
Choi, Mi-Jung
Paek, Kyung Shin
Lim, Dae-Seog
Seo, Han Geuk
author_facet Kang, Eun Sil
Hwang, Jung Seok
Lee, Won Jin
Lee, Gyeong Hee
Choi, Mi-Jung
Paek, Kyung Shin
Lim, Dae-Seog
Seo, Han Geuk
author_sort Kang, Eun Sil
collection PubMed
description We investigated the effect of peroxisome proliferator-activated receptor δ (PPARδ) on angiotensin II (Ang II)-triggered hypertrophy of vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand of PPARδ, significantly inhibited Ang II-stimulated protein synthesis in a concentration-dependent manner, as determined by [(3)H]-leucine incorporation. GW501516-activated PPARδ also suppressed Ang II-induced generation of reactive oxygen species (ROS) in VSMCs. Transfection of small interfering RNA (siRNA) against PPARδ significantly reversed the effects of GW501516 on [(3)H]-leucine incorporation and ROS generation, indicating that PPARδ is involved in these effects. By contrast, these GW501516-mediated actions were potentiated in VSMCs transfected with siRNA against NADPH oxidase (NOX) 1 or 4, suggesting that ligand-activated PPARδ elicits these effects by modulating NOX-mediated ROS generation. The phosphatidylinositol 3-kinase inhibitor LY294002 also inhibited Ang II-stimulated [(3)H]-leucine incorporation and ROS generation by preventing membrane translocation of Rac1. These observations suggest that PPARδ is an endogenous modulator of Ang II-triggered hypertrophy of VSMCs, and is thus a potential target to treat vascular diseases associated with hypertrophic changes of VSMCs.
format Online
Article
Text
id pubmed-6324793
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-63247932019-01-19 Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS Kang, Eun Sil Hwang, Jung Seok Lee, Won Jin Lee, Gyeong Hee Choi, Mi-Jung Paek, Kyung Shin Lim, Dae-Seog Seo, Han Geuk PLoS One Research Article We investigated the effect of peroxisome proliferator-activated receptor δ (PPARδ) on angiotensin II (Ang II)-triggered hypertrophy of vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand of PPARδ, significantly inhibited Ang II-stimulated protein synthesis in a concentration-dependent manner, as determined by [(3)H]-leucine incorporation. GW501516-activated PPARδ also suppressed Ang II-induced generation of reactive oxygen species (ROS) in VSMCs. Transfection of small interfering RNA (siRNA) against PPARδ significantly reversed the effects of GW501516 on [(3)H]-leucine incorporation and ROS generation, indicating that PPARδ is involved in these effects. By contrast, these GW501516-mediated actions were potentiated in VSMCs transfected with siRNA against NADPH oxidase (NOX) 1 or 4, suggesting that ligand-activated PPARδ elicits these effects by modulating NOX-mediated ROS generation. The phosphatidylinositol 3-kinase inhibitor LY294002 also inhibited Ang II-stimulated [(3)H]-leucine incorporation and ROS generation by preventing membrane translocation of Rac1. These observations suggest that PPARδ is an endogenous modulator of Ang II-triggered hypertrophy of VSMCs, and is thus a potential target to treat vascular diseases associated with hypertrophic changes of VSMCs. Public Library of Science 2019-01-08 /pmc/articles/PMC6324793/ /pubmed/30620754 http://dx.doi.org/10.1371/journal.pone.0210482 Text en © 2019 Kang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kang, Eun Sil
Hwang, Jung Seok
Lee, Won Jin
Lee, Gyeong Hee
Choi, Mi-Jung
Paek, Kyung Shin
Lim, Dae-Seog
Seo, Han Geuk
Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS
title Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS
title_full Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS
title_fullStr Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS
title_full_unstemmed Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS
title_short Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS
title_sort ligand-activated pparδ inhibits angiotensin ii-stimulated hypertrophy of vascular smooth muscle cells by targeting ros
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324793/
https://www.ncbi.nlm.nih.gov/pubmed/30620754
http://dx.doi.org/10.1371/journal.pone.0210482
work_keys_str_mv AT kangeunsil ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT hwangjungseok ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT leewonjin ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT leegyeonghee ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT choimijung ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT paekkyungshin ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT limdaeseog ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros
AT seohangeuk ligandactivatedppardinhibitsangiotensiniistimulatedhypertrophyofvascularsmoothmusclecellsbytargetingros