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Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells

Aging, obesity, hypertension, and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing, and bioinformatic methods to investigate the common effects of CVD risk factors in mouse c...

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Autores principales: Hemanthakumar, Karthik Amudhala, Fang, Shentong, Anisimov, Andrey, Mäyränpää, Mikko I, Mervaala, Eero, Kivelä, Riikka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043751/
https://www.ncbi.nlm.nih.gov/pubmed/33661096
http://dx.doi.org/10.7554/eLife.62678
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author Hemanthakumar, Karthik Amudhala
Fang, Shentong
Anisimov, Andrey
Mäyränpää, Mikko I
Mervaala, Eero
Kivelä, Riikka
author_facet Hemanthakumar, Karthik Amudhala
Fang, Shentong
Anisimov, Andrey
Mäyränpää, Mikko I
Mervaala, Eero
Kivelä, Riikka
author_sort Hemanthakumar, Karthik Amudhala
collection PubMed
description Aging, obesity, hypertension, and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing, and bioinformatic methods to investigate the common effects of CVD risk factors in mouse cardiac endothelial cells (ECs). Aging, obesity, and pressure overload all upregulated pathways related to TGF-β signaling and mesenchymal gene expression, inflammation, vascular permeability, oxidative stress, collagen synthesis, and cellular senescence, whereas exercise training attenuated most of the same pathways. We identified collagen chaperone Serpinh1 (also called as Hsp47) to be significantly increased by aging and obesity and repressed by exercise training. Mechanistic studies demonstrated that increased SERPINH1 in human ECs induced mesenchymal properties, while its silencing inhibited collagen deposition. Our data demonstrate that CVD risk factors significantly remodel the transcriptomic landscape of cardiac ECs inducing inflammatory, senescence, and mesenchymal features. SERPINH1 was identified as a potential therapeutic target in ECs.
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spelling pubmed-80437512021-04-21 Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells Hemanthakumar, Karthik Amudhala Fang, Shentong Anisimov, Andrey Mäyränpää, Mikko I Mervaala, Eero Kivelä, Riikka eLife Chromosomes and Gene Expression Aging, obesity, hypertension, and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing, and bioinformatic methods to investigate the common effects of CVD risk factors in mouse cardiac endothelial cells (ECs). Aging, obesity, and pressure overload all upregulated pathways related to TGF-β signaling and mesenchymal gene expression, inflammation, vascular permeability, oxidative stress, collagen synthesis, and cellular senescence, whereas exercise training attenuated most of the same pathways. We identified collagen chaperone Serpinh1 (also called as Hsp47) to be significantly increased by aging and obesity and repressed by exercise training. Mechanistic studies demonstrated that increased SERPINH1 in human ECs induced mesenchymal properties, while its silencing inhibited collagen deposition. Our data demonstrate that CVD risk factors significantly remodel the transcriptomic landscape of cardiac ECs inducing inflammatory, senescence, and mesenchymal features. SERPINH1 was identified as a potential therapeutic target in ECs. eLife Sciences Publications, Ltd 2021-03-04 /pmc/articles/PMC8043751/ /pubmed/33661096 http://dx.doi.org/10.7554/eLife.62678 Text en © 2021, Hemanthakumar et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Hemanthakumar, Karthik Amudhala
Fang, Shentong
Anisimov, Andrey
Mäyränpää, Mikko I
Mervaala, Eero
Kivelä, Riikka
Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
title Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
title_full Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
title_fullStr Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
title_full_unstemmed Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
title_short Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
title_sort cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043751/
https://www.ncbi.nlm.nih.gov/pubmed/33661096
http://dx.doi.org/10.7554/eLife.62678
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