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TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome

Formation of aortic aneurysms as a consequence of augmented transforming growth factor β (TGF-β) signaling and vascular smooth muscle cell (VSMC) dysfunction is a potentially lethal complication of Marfan syndrome (MFS). Here, we examined VSMC senescence in patients with MFS and explored the potenti...

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Autores principales: You, Wei, Hong, Yimei, He, Haiwei, Huang, Xiaoran, Tao, Wuyuan, Liang, Xiaoting, Zhang, Yuelin, Li, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594817/
https://www.ncbi.nlm.nih.gov/pubmed/31147528
http://dx.doi.org/10.18632/aging.101998
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author You, Wei
Hong, Yimei
He, Haiwei
Huang, Xiaoran
Tao, Wuyuan
Liang, Xiaoting
Zhang, Yuelin
Li, Xin
author_facet You, Wei
Hong, Yimei
He, Haiwei
Huang, Xiaoran
Tao, Wuyuan
Liang, Xiaoting
Zhang, Yuelin
Li, Xin
author_sort You, Wei
collection PubMed
description Formation of aortic aneurysms as a consequence of augmented transforming growth factor β (TGF-β) signaling and vascular smooth muscle cell (VSMC) dysfunction is a potentially lethal complication of Marfan syndrome (MFS). Here, we examined VSMC senescence in patients with MFS and explored the potential mechanisms that link VSMC senescence and TGF-β. Tissue was harvested from the ascending aorta of control donors and MFS patients, and VSMCs were isolated. Senescence-associated β-galactosidase (SA-β-gal) activity and expression of senescence-related proteins (p53, p21) were significantly higher in aneurysmal tissue from MFS patients than in healthy aortic tissue from control donors. Compared to control-VSMCs, MFS-VSMCs were larger with higher levels of both SA-β-gal activity and mitochondrial reactive oxygen species (ROS). In addition, TGF-β1 levels were much higher in MFS- than control-VSMCs. TGF-β1 induced VSMC senescence through excessive ROS generation. This effect was suppressed by Mito-tempo, a mitochondria-targeted antioxidant, or SC-514, a NF-κB inhibitor. This suggests TGF-β1 induces VSMC senescence through ROS-mediated activation of NF-κB signaling. It thus appears that a TGF-β1/ROS/NF-κB axis may mediate VSMC senescence and aneurysm formation in MFS patients. This finding could serve as the basis for a novel strategy for treating aortic aneurysm in MFS.
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spelling pubmed-65948172019-07-01 TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome You, Wei Hong, Yimei He, Haiwei Huang, Xiaoran Tao, Wuyuan Liang, Xiaoting Zhang, Yuelin Li, Xin Aging (Albany NY) Research Paper Formation of aortic aneurysms as a consequence of augmented transforming growth factor β (TGF-β) signaling and vascular smooth muscle cell (VSMC) dysfunction is a potentially lethal complication of Marfan syndrome (MFS). Here, we examined VSMC senescence in patients with MFS and explored the potential mechanisms that link VSMC senescence and TGF-β. Tissue was harvested from the ascending aorta of control donors and MFS patients, and VSMCs were isolated. Senescence-associated β-galactosidase (SA-β-gal) activity and expression of senescence-related proteins (p53, p21) were significantly higher in aneurysmal tissue from MFS patients than in healthy aortic tissue from control donors. Compared to control-VSMCs, MFS-VSMCs were larger with higher levels of both SA-β-gal activity and mitochondrial reactive oxygen species (ROS). In addition, TGF-β1 levels were much higher in MFS- than control-VSMCs. TGF-β1 induced VSMC senescence through excessive ROS generation. This effect was suppressed by Mito-tempo, a mitochondria-targeted antioxidant, or SC-514, a NF-κB inhibitor. This suggests TGF-β1 induces VSMC senescence through ROS-mediated activation of NF-κB signaling. It thus appears that a TGF-β1/ROS/NF-κB axis may mediate VSMC senescence and aneurysm formation in MFS patients. This finding could serve as the basis for a novel strategy for treating aortic aneurysm in MFS. Impact Journals 2019-05-30 /pmc/articles/PMC6594817/ /pubmed/31147528 http://dx.doi.org/10.18632/aging.101998 Text en Copyright © 2019 You et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
You, Wei
Hong, Yimei
He, Haiwei
Huang, Xiaoran
Tao, Wuyuan
Liang, Xiaoting
Zhang, Yuelin
Li, Xin
TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
title TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
title_full TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
title_fullStr TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
title_full_unstemmed TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
title_short TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
title_sort tgf-β mediates aortic smooth muscle cell senescence in marfan syndrome
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594817/
https://www.ncbi.nlm.nih.gov/pubmed/31147528
http://dx.doi.org/10.18632/aging.101998
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