Author:
Bizou Mathilde,Itier Romain,Majdoubi Mina,Abbadi Dounia,Pichery Estelle,Dutaur Marianne,Marsal Dimitri,Calise Denis,Garmy-Susini Barbara,Douin-Echinard Victorine,Roncalli Jérome,Parini Angelo,Pizzinat Nathalie
Abstract
AbstractThe lymphatic network of mammalian heart is an important regulator of interstitial fluid compartment and immune cell trafficking. We observed a remodeling of the cardiac lymphatic vessels and a reduced lymphatic efficiency during heart hypertrophy and failure induced by transverse aortic constriction. The lymphatic endothelial cell number of the failing hearts was positively correlated with cardiac function and with a subset of cardiac macrophages. This macrophage population distinguished by LYVE-1 (Lymphatic vessel endothelial hyaluronic acid receptor-1) and by resident macrophage gene expression signature, appeared not replenished by CCR2 mediated monocyte infiltration during pressure overload. Isolation of macrophage subpopulations showed that the LYVE-1 positive subset sustained in vitro and in vivo lymphangiogenesis through the expression of pro-lymphangiogenic factors. In contrast, the LYVE-1 negative macrophage subset strongly expressed MMP12 and decreased the endothelial LYVE-1 receptors in lymphatic endothelial cells, a feature of cardiac lymphatic remodeling in failing hearts. The treatment of mice with a CCR2 antagonist during pressure overload modified the proportion of macrophage subsets within the pathological heart and preserved lymphatic network from remodeling. This study reports unknown and differential functions of macrophage subpopulations in the regulation of cardiac lymphatic during pathological hypertrophy and may constitute a key mechanism underlying the progression of heart failure.
Funder
Société Française de Cardiologie
INSERM
Publisher
Springer Science and Business Media LLC
Reference47 articles.
1. Laine, G. A. & Allen, S. J. Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circ. Res. 68, 1713–1721 (1991).
2. Kong, D., Kong, X. & Wang, L. Effect of cardiac lymph flow obstruction on cardiac collagen synthesis and interstitial fibrosis. Physiol. Res. 55, 253–258 (2006).
3. Ludwig, L. L. et al. Impairment of left ventricular function by acute cardiac lymphatic obstruction. Cardiovasc. Res. 33, 164–171 (1997).
4. Vieira, J. M. et al. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J. Clin. Investig. https://doi.org/10.1172/JCI97192 (2018).
5. Henri, O. et al. Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction. Circulation 133, 1484–1497 (2016) (discussion 1497).
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