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Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways

The aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks’ pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone fo...

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Autores principales: Kubota, Tetsuya, Kubota, Naoto, Sato, Hiroyuki, Inoue, Mariko, Kumagai, Hiroki, Iwamura, Tomokatsu, Takamoto, Iseki, Kobayashi, Tsuneo, Moroi, Masao, Terauchi, Yasuo, Tobe, Kazuyuki, Ueki, Kohjiro, Kadowaki, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050439/
https://www.ncbi.nlm.nih.gov/pubmed/27703271
http://dx.doi.org/10.1038/srep34707
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author Kubota, Tetsuya
Kubota, Naoto
Sato, Hiroyuki
Inoue, Mariko
Kumagai, Hiroki
Iwamura, Tomokatsu
Takamoto, Iseki
Kobayashi, Tsuneo
Moroi, Masao
Terauchi, Yasuo
Tobe, Kazuyuki
Ueki, Kohjiro
Kadowaki, Takashi
author_facet Kubota, Tetsuya
Kubota, Naoto
Sato, Hiroyuki
Inoue, Mariko
Kumagai, Hiroki
Iwamura, Tomokatsu
Takamoto, Iseki
Kobayashi, Tsuneo
Moroi, Masao
Terauchi, Yasuo
Tobe, Kazuyuki
Ueki, Kohjiro
Kadowaki, Takashi
author_sort Kubota, Tetsuya
collection PubMed
description The aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks’ pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced neointimal formation in the WT mice with upregulation of the plasma adiponectin levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting that pioglitazone suppressed neointimal formation by adiponectin-dependent mechanisms. Pioglitazone for 3 weeks suppressed vascular smooth muscle cell (VSMC) proliferation and increased AdipoR2 expression in the WT mice. In vitro, globular adiponectin activated AMPK through both AdipoR1 and AdipoR2, resulting in the inhibition of VSMC proliferation. Interestingly, 8-weeks’ pioglitazone was reduced neointimal formation in APN-KO mice to degree similar to that seen in the WT mice, suggesting that pioglitazone can also suppress neointimal formation via a mechanism independent of adiponectin. Pioglitazone for 8 weeks completely abrogated the increased VSMC proliferation, along with a reduction of cyclin B1 and cyclin D1 expressions and cardiovascular risk profile in the APN-KO mice. In vitro, pioglitazone suppressed these expressions, leading to inhibition of VSMC proliferation. Pioglitazone suppresses neointimal formation via both adiponectin-dependent and adiponectin-independent mechanisms.
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spelling pubmed-50504392016-10-11 Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways Kubota, Tetsuya Kubota, Naoto Sato, Hiroyuki Inoue, Mariko Kumagai, Hiroki Iwamura, Tomokatsu Takamoto, Iseki Kobayashi, Tsuneo Moroi, Masao Terauchi, Yasuo Tobe, Kazuyuki Ueki, Kohjiro Kadowaki, Takashi Sci Rep Article The aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks’ pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced neointimal formation in the WT mice with upregulation of the plasma adiponectin levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting that pioglitazone suppressed neointimal formation by adiponectin-dependent mechanisms. Pioglitazone for 3 weeks suppressed vascular smooth muscle cell (VSMC) proliferation and increased AdipoR2 expression in the WT mice. In vitro, globular adiponectin activated AMPK through both AdipoR1 and AdipoR2, resulting in the inhibition of VSMC proliferation. Interestingly, 8-weeks’ pioglitazone was reduced neointimal formation in APN-KO mice to degree similar to that seen in the WT mice, suggesting that pioglitazone can also suppress neointimal formation via a mechanism independent of adiponectin. Pioglitazone for 8 weeks completely abrogated the increased VSMC proliferation, along with a reduction of cyclin B1 and cyclin D1 expressions and cardiovascular risk profile in the APN-KO mice. In vitro, pioglitazone suppressed these expressions, leading to inhibition of VSMC proliferation. Pioglitazone suppresses neointimal formation via both adiponectin-dependent and adiponectin-independent mechanisms. Nature Publishing Group 2016-10-05 /pmc/articles/PMC5050439/ /pubmed/27703271 http://dx.doi.org/10.1038/srep34707 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kubota, Tetsuya
Kubota, Naoto
Sato, Hiroyuki
Inoue, Mariko
Kumagai, Hiroki
Iwamura, Tomokatsu
Takamoto, Iseki
Kobayashi, Tsuneo
Moroi, Masao
Terauchi, Yasuo
Tobe, Kazuyuki
Ueki, Kohjiro
Kadowaki, Takashi
Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
title Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
title_full Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
title_fullStr Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
title_full_unstemmed Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
title_short Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
title_sort pioglitazone ameliorates smooth muscle cell proliferation in cuff-induced neointimal formation by both adiponectin-dependent and -independent pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050439/
https://www.ncbi.nlm.nih.gov/pubmed/27703271
http://dx.doi.org/10.1038/srep34707
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