Cargando…

Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway

Sestrin2 (Sesn2) is involved in the progression of cardiovascular diseases, such as hypertension and myocardial infarction. This study aimed to examine Sesn2 expression in human calcific aortic valve disease (CAVD) and explore its possible mechanisms by which Sesn2 participates in this process. CAVD...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Haixiong, Xi, Jicheng, Zhang, Zhibiao, Li, Jun, Guo, Liping, Li, Na, Sun, Yuehui, Li, Xiaofang, Han, Xuebin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Journal of Cardiovascular Pharmacology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536529/
https://www.ncbi.nlm.nih.gov/pubmed/35881902
http://dx.doi.org/10.1097/FJC.0000000000001314
_version_ 1784802999334338560
author Wang, Haixiong
Xi, Jicheng
Zhang, Zhibiao
Li, Jun
Guo, Liping
Li, Na
Sun, Yuehui
Li, Xiaofang
Han, Xuebin
author_facet Wang, Haixiong
Xi, Jicheng
Zhang, Zhibiao
Li, Jun
Guo, Liping
Li, Na
Sun, Yuehui
Li, Xiaofang
Han, Xuebin
author_sort Wang, Haixiong
collection PubMed
description Sestrin2 (Sesn2) is involved in the progression of cardiovascular diseases, such as hypertension and myocardial infarction. This study aimed to examine Sesn2 expression in human calcific aortic valve disease (CAVD) and explore its possible mechanisms by which Sesn2 participates in this process. CAVD and normal aortic valves were collected. Sesn2 expression and sources were examined, and the results showed that Sesn2 expression was increased in aortic valves from patients with CAVD and was mainly secreted by macrophages. Additionally, U937 macrophages were pretreated with si-Sesn2 or cDNA-Sesn2 and further treated with oxidized low-density lipoprotein (ox-LDL); M1 macrophages and their markers were measured, and we found that pretreatment with si-Sesn2 increased ox-LDL–induced M1 macrophage polarization and marker mRNA levels, whereas pretreatment with cDNA-Sesn2 had the opposite effects. In ox-LDL–treated U937 macrophages, oxidative stress levels were increased in the si-Sesn2 pretreatment group and further increased by si-Nrf2 treatment, whereas oxidative stress levels were decreased in the cDNA-Sesn2 pretreatment group and significantly reversed by ML385, a specific Nrf2 inhibitor. The effects of Sesn2 on ox-LDL-induced oxidative stress and the osteogenic differentiation of ox-LDL-induced valvular interstitial cells (VICs) was examined by down-regulating Nrf2 pathway. When U937 macrophages were co-cultured with VICs, downregulation of Sesn2 increased ox-LDL-induced osteogenic differentiation in VICs, whereas overexpression of Sesn2 exerted the opposite effects. Our study suggests that Sesn2 is increased in CAVD aortic valves and may participate in the development of CAVD by regulating oxidative stress via the Nrf2 pathway.
format Online
Article
Text
id pubmed-9536529
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Journal of Cardiovascular Pharmacology
record_format MEDLINE/PubMed
spelling pubmed-95365292022-10-11 Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway Wang, Haixiong Xi, Jicheng Zhang, Zhibiao Li, Jun Guo, Liping Li, Na Sun, Yuehui Li, Xiaofang Han, Xuebin J Cardiovasc Pharmacol Original Article Sestrin2 (Sesn2) is involved in the progression of cardiovascular diseases, such as hypertension and myocardial infarction. This study aimed to examine Sesn2 expression in human calcific aortic valve disease (CAVD) and explore its possible mechanisms by which Sesn2 participates in this process. CAVD and normal aortic valves were collected. Sesn2 expression and sources were examined, and the results showed that Sesn2 expression was increased in aortic valves from patients with CAVD and was mainly secreted by macrophages. Additionally, U937 macrophages were pretreated with si-Sesn2 or cDNA-Sesn2 and further treated with oxidized low-density lipoprotein (ox-LDL); M1 macrophages and their markers were measured, and we found that pretreatment with si-Sesn2 increased ox-LDL–induced M1 macrophage polarization and marker mRNA levels, whereas pretreatment with cDNA-Sesn2 had the opposite effects. In ox-LDL–treated U937 macrophages, oxidative stress levels were increased in the si-Sesn2 pretreatment group and further increased by si-Nrf2 treatment, whereas oxidative stress levels were decreased in the cDNA-Sesn2 pretreatment group and significantly reversed by ML385, a specific Nrf2 inhibitor. The effects of Sesn2 on ox-LDL-induced oxidative stress and the osteogenic differentiation of ox-LDL-induced valvular interstitial cells (VICs) was examined by down-regulating Nrf2 pathway. When U937 macrophages were co-cultured with VICs, downregulation of Sesn2 increased ox-LDL-induced osteogenic differentiation in VICs, whereas overexpression of Sesn2 exerted the opposite effects. Our study suggests that Sesn2 is increased in CAVD aortic valves and may participate in the development of CAVD by regulating oxidative stress via the Nrf2 pathway. Journal of Cardiovascular Pharmacology 2022-10 2022-06-14 /pmc/articles/PMC9536529/ /pubmed/35881902 http://dx.doi.org/10.1097/FJC.0000000000001314 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Original Article
Wang, Haixiong
Xi, Jicheng
Zhang, Zhibiao
Li, Jun
Guo, Liping
Li, Na
Sun, Yuehui
Li, Xiaofang
Han, Xuebin
Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
title Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
title_full Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
title_fullStr Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
title_full_unstemmed Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
title_short Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
title_sort sestrin2 is increased in calcific aortic disease and inhibits osteoblastic differentiation in valvular interstitial cells via the nuclear factor e2–related factor 2 pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536529/
https://www.ncbi.nlm.nih.gov/pubmed/35881902
http://dx.doi.org/10.1097/FJC.0000000000001314
work_keys_str_mv AT wanghaixiong sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT xijicheng sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT zhangzhibiao sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT lijun sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT guoliping sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT lina sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT sunyuehui sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT lixiaofang sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway
AT hanxuebin sestrin2isincreasedincalcificaorticdiseaseandinhibitsosteoblasticdifferentiationinvalvularinterstitialcellsviathenuclearfactore2relatedfactor2pathway