Author:
Flamant M.,Mougenot N.,Balse E.,Le Fèvre L.,Atassi F.,Gautier E. L.,Le Goff W.,Keck M.,Nadaud S.,Combadière C.,Boissonnas A.,Pavoine C.
Abstract
AbstractWe 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.
Funder
Institute of cardiometabolism and nutrition (ICAN innovative seeding project
Publisher
Springer Science and Business Media LLC
Reference44 articles.
1. Mozaffarian, D. et al. Heart disease and stroke statistics–2015 update: A report from the American Heart Association. Circulation 131, e29-322 (2015).
2. Fujiu, K. et al. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation. Nat. Med. 23, 611–622 (2017).
3. Silljé, H. H. W. & de Boer, R. A. Heart failure: Macrophages take centre stage in the heart–brain–kidney axis. Nat. Rev. Nephrol. 13, 388–390 (2017).
4. Badenhorst, D. et al. β-adrenergic activation initiates chamber dilatation in concentric hypertrophy. Hypertension 41, 499–504 (2003).
5. Balakumar, P. & Jagadeesh, G. Multifarious molecular signaling cascades of cardiac hypertrophy: Can the muddy waters be cleared?. Pharmacol. Res. 62, 365–383 (2010).
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献