Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure

Abstract We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early β-adrenergic stimulation. He...

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Autores principales:	M. Flamant, N. Mougenot, E. Balse, L. Le Fèvre, F. Atassi, E. L. Gautier, W. Le Goff, M. Keck, S. Nadaud, C. Combadière, A. Boissonnas, C. Pavoine
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77862c2added47309a8996ae9920ed7a
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spelling	oai:doaj.org-article:77862c2added47309a8996ae9920ed7a2021-12-02T17:19:15ZEarly activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure10.1038/s41598-021-97493-z2045-2322https://doaj.org/article/77862c2added47309a8996ae9920ed7a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97493-zhttps://doaj.org/toc/2045-2322Abstract We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early β-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF. Combining transcriptomic and secretomic approaches we characterized Mφ-enriched CD45+ cells from ECH hearts as CX3CL1- and TNFα-secreting cells. In-vivo experiments, using intramyocardial injection in ECH hearts of either Cx3cl1 or Cx3cr1 siRNA, or Cx3cr1 −/− knockout mice, identified the CX3CL1/CX3CR1 axis as a protective pathway delaying transition to HF. In-vitro results showed that CX3CL1 not only enhanced ECH Mφ proliferation and expansion but also supported adult cardiomyocyte hypertrophy via a synergistic action with TNFα. Our data underscore the in-vivo transient protective role of the CX3CL1/CX3CR1 axis in ECH remodeling and suggest the participation of CX3CL1-secreting Mφ and their crosstalk with CX3CR1-expressing cardiomyocytes to delay HF.M. FlamantN. MougenotE. BalseL. Le FèvreF. AtassiE. L. GautierW. Le GoffM. KeckS. NadaudC. CombadièreA. BoissonnasC. PavoineNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. Flamant N. Mougenot E. Balse L. Le Fèvre F. Atassi E. L. Gautier W. Le Goff M. Keck S. Nadaud C. Combadière A. Boissonnas C. Pavoine Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
description	Abstract We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early β-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF. Combining transcriptomic and secretomic approaches we characterized Mφ-enriched CD45+ cells from ECH hearts as CX3CL1- and TNFα-secreting cells. In-vivo experiments, using intramyocardial injection in ECH hearts of either Cx3cl1 or Cx3cr1 siRNA, or Cx3cr1 −/− knockout mice, identified the CX3CL1/CX3CR1 axis as a protective pathway delaying transition to HF. In-vitro results showed that CX3CL1 not only enhanced ECH Mφ proliferation and expansion but also supported adult cardiomyocyte hypertrophy via a synergistic action with TNFα. Our data underscore the in-vivo transient protective role of the CX3CL1/CX3CR1 axis in ECH remodeling and suggest the participation of CX3CL1-secreting Mφ and their crosstalk with CX3CR1-expressing cardiomyocytes to delay HF.
format	article
author	M. Flamant N. Mougenot E. Balse L. Le Fèvre F. Atassi E. L. Gautier W. Le Goff M. Keck S. Nadaud C. Combadière A. Boissonnas C. Pavoine
author_facet	M. Flamant N. Mougenot E. Balse L. Le Fèvre F. Atassi E. L. Gautier W. Le Goff M. Keck S. Nadaud C. Combadière A. Boissonnas C. Pavoine
author_sort	M. Flamant
title	Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
title_short	Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
title_full	Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
title_fullStr	Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
title_full_unstemmed	Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
title_sort	early activation of the cardiac cx3cl1/cx3cr1 axis delays β-adrenergic-induced heart failure
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/77862c2added47309a8996ae9920ed7a
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Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure

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