Cargando…

Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism

BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves mon...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Jingyuan, Luo, Jun, Qiu, Haihua, Tang, Yi, Yang, Xiaojie, Chen, Yusi, Li, Zilu, Li, Jiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358849/
https://www.ncbi.nlm.nih.gov/pubmed/35941581
http://dx.doi.org/10.1186/s12944-022-01680-4
_version_ 1784764016928751616
author Chen, Jingyuan
Luo, Jun
Qiu, Haihua
Tang, Yi
Yang, Xiaojie
Chen, Yusi
Li, Zilu
Li, Jiang
author_facet Chen, Jingyuan
Luo, Jun
Qiu, Haihua
Tang, Yi
Yang, Xiaojie
Chen, Yusi
Li, Zilu
Li, Jiang
author_sort Chen, Jingyuan
collection PubMed
description BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. METHODS: ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit‐8 and 5‐ethynyl‐2'‐deoxyuridine5‐ethynyl‐2'‐deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. RESULTS: ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. CONCLUSION: ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-022-01680-4.
format Online
Article
Text
id pubmed-9358849
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-93588492022-08-10 Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism Chen, Jingyuan Luo, Jun Qiu, Haihua Tang, Yi Yang, Xiaojie Chen, Yusi Li, Zilu Li, Jiang Lipids Health Dis Research BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. METHODS: ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit‐8 and 5‐ethynyl‐2'‐deoxyuridine5‐ethynyl‐2'‐deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. RESULTS: ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. CONCLUSION: ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-022-01680-4. BioMed Central 2022-08-08 /pmc/articles/PMC9358849/ /pubmed/35941581 http://dx.doi.org/10.1186/s12944-022-01680-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Jingyuan
Luo, Jun
Qiu, Haihua
Tang, Yi
Yang, Xiaojie
Chen, Yusi
Li, Zilu
Li, Jiang
Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
title Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
title_full Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
title_fullStr Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
title_full_unstemmed Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
title_short Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
title_sort apolipoprotein a5 ameliorates mct induced pulmonary hypertension by inhibiting er stress in a grp78 dependent mechanism
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358849/
https://www.ncbi.nlm.nih.gov/pubmed/35941581
http://dx.doi.org/10.1186/s12944-022-01680-4
work_keys_str_mv AT chenjingyuan apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT luojun apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT qiuhaihua apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT tangyi apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT yangxiaojie apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT chenyusi apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT lizilu apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism
AT lijiang apolipoproteina5amelioratesmctinducedpulmonaryhypertensionbyinhibitingerstressinagrp78dependentmechanism