Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall

Abstract Numerous recent studies have shown that in the continuum of cardiovascular diseases, the measurement of arterial stiffness has powerful predictive value in cardiovascular risk and mortality and that this value is independent of other conventional risk factors, such as age, cholesterol level...

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Autores principales:	Beatrice Romier, Cédric Dray, Laetitia Vanalderwiert, Amandine Wahart, Thinhinane Hocine, Alizée Dortignac, Christian Garbar, Corinne Garbar, Camille Boulagnon, Nicole Bouland, Pascal Maurice, Amar Bennasroune, Hervé Sartelet, Laurent Martiny, Laurent Duca, Philippe Valet, Sébastien Blaise
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2f042d2a1b247e4ba7400a658c1b047
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spelling	oai:doaj.org-article:a2f042d2a1b247e4ba7400a658c1b0472021-11-21T12:21:04ZApelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall10.1038/s41598-021-01735-z2045-2322https://doaj.org/article/a2f042d2a1b247e4ba7400a658c1b0472021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01735-zhttps://doaj.org/toc/2045-2322Abstract Numerous recent studies have shown that in the continuum of cardiovascular diseases, the measurement of arterial stiffness has powerful predictive value in cardiovascular risk and mortality and that this value is independent of other conventional risk factors, such as age, cholesterol levels, diabetes, smoking, or average blood pressure. Vascular stiffening is often the main cause of arterial hypertension (AHT), which is common in the presence of obesity. However, the mechanisms leading to vascular stiffening, as well as preventive factors, remain unclear. The aim of the present study was to investigate the consequences of apelin deficiency on the vascular stiffening and wall remodeling of aorta in mice. This factor freed by visceral adipose tissue, is known for its homeostasic role in lipid and vascular metabolisms, or again in inflammation. We compared the level of metabolic markers, inflammation of white adipose tissue (WAT), and aortic wall remodeling from functional and structural approaches in apelin-deficient and wild-type (WT) mice. Apelin-deficient mice were generated by knockout of the apelin gene (APL-KO). From 8 mice by groups, aortic stiffness was analyzed by pulse wave velocity measurements and by characterizations of collagen and elastic fibers. Mann–Whitney statistical test determined the significant data (p < 5%) between groups. The APL-KO mice developed inflammation, which was associated with significant remodeling of visceral WAT, such as neutrophil elastase and cathepsin S expressions. In vitro, cathepsin S activity was detected in conditioned medium prepared from adipose tissue of the APL-KO mice, and cathepsin S activity induced high fragmentations of elastic fiber of wild-type aorta, suggesting that the WAT secretome could play a major role in vascular stiffening. In vivo, remodeling of the extracellular matrix (ECM), such as collagen accumulation and elastolysis, was observed in the aortic walls of the APL-KO mice, with the latter associated with high cathepsin S activity. In addition, pulse wave velocity (PWV) and AHT were increased in the APL-KO mice. The latter could explain aortic wall remodeling in the APL-KO mice. The absence of apelin expression, particularly in WAT, modified the adipocyte secretome and facilitated remodeling of the ECM of the aortic wall. Thus, elastolysis of elastic fibers and collagen accumulation contributed to vascular stiffening and AHT. Therefore, apelin expression could be a major element to preserve vascular homeostasis.Beatrice RomierCédric DrayLaetitia VanalderwiertAmandine WahartThinhinane HocineAlizée DortignacChristian GarbarCorinne GarbarCamille BoulagnonNicole BoulandPascal MauriceAmar BennasrouneHervé SarteletLaurent MartinyLaurent DucaPhilippe ValetSébastien BlaiseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beatrice Romier Cédric Dray Laetitia Vanalderwiert Amandine Wahart Thinhinane Hocine Alizée Dortignac Christian Garbar Corinne Garbar Camille Boulagnon Nicole Bouland Pascal Maurice Amar Bennasroune Hervé Sartelet Laurent Martiny Laurent Duca Philippe Valet Sébastien Blaise Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
description	Abstract Numerous recent studies have shown that in the continuum of cardiovascular diseases, the measurement of arterial stiffness has powerful predictive value in cardiovascular risk and mortality and that this value is independent of other conventional risk factors, such as age, cholesterol levels, diabetes, smoking, or average blood pressure. Vascular stiffening is often the main cause of arterial hypertension (AHT), which is common in the presence of obesity. However, the mechanisms leading to vascular stiffening, as well as preventive factors, remain unclear. The aim of the present study was to investigate the consequences of apelin deficiency on the vascular stiffening and wall remodeling of aorta in mice. This factor freed by visceral adipose tissue, is known for its homeostasic role in lipid and vascular metabolisms, or again in inflammation. We compared the level of metabolic markers, inflammation of white adipose tissue (WAT), and aortic wall remodeling from functional and structural approaches in apelin-deficient and wild-type (WT) mice. Apelin-deficient mice were generated by knockout of the apelin gene (APL-KO). From 8 mice by groups, aortic stiffness was analyzed by pulse wave velocity measurements and by characterizations of collagen and elastic fibers. Mann–Whitney statistical test determined the significant data (p < 5%) between groups. The APL-KO mice developed inflammation, which was associated with significant remodeling of visceral WAT, such as neutrophil elastase and cathepsin S expressions. In vitro, cathepsin S activity was detected in conditioned medium prepared from adipose tissue of the APL-KO mice, and cathepsin S activity induced high fragmentations of elastic fiber of wild-type aorta, suggesting that the WAT secretome could play a major role in vascular stiffening. In vivo, remodeling of the extracellular matrix (ECM), such as collagen accumulation and elastolysis, was observed in the aortic walls of the APL-KO mice, with the latter associated with high cathepsin S activity. In addition, pulse wave velocity (PWV) and AHT were increased in the APL-KO mice. The latter could explain aortic wall remodeling in the APL-KO mice. The absence of apelin expression, particularly in WAT, modified the adipocyte secretome and facilitated remodeling of the ECM of the aortic wall. Thus, elastolysis of elastic fibers and collagen accumulation contributed to vascular stiffening and AHT. Therefore, apelin expression could be a major element to preserve vascular homeostasis.
format	article
author	Beatrice Romier Cédric Dray Laetitia Vanalderwiert Amandine Wahart Thinhinane Hocine Alizée Dortignac Christian Garbar Corinne Garbar Camille Boulagnon Nicole Bouland Pascal Maurice Amar Bennasroune Hervé Sartelet Laurent Martiny Laurent Duca Philippe Valet Sébastien Blaise
author_facet	Beatrice Romier Cédric Dray Laetitia Vanalderwiert Amandine Wahart Thinhinane Hocine Alizée Dortignac Christian Garbar Corinne Garbar Camille Boulagnon Nicole Bouland Pascal Maurice Amar Bennasroune Hervé Sartelet Laurent Martiny Laurent Duca Philippe Valet Sébastien Blaise
author_sort	Beatrice Romier
title	Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
title_short	Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
title_full	Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
title_fullStr	Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
title_full_unstemmed	Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
title_sort	apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a2f042d2a1b247e4ba7400a658c1b047
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Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall

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