Cardiac macrophages promote diastolic dysfunction

Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac ma...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2018-02, Vol.215 (2), p.423-440
Main Authors: Hulsmans, Maarten, Sager, Hendrik B, Roh, Jason D, Valero-Muñoz, María, Houstis, Nicholas E, Iwamoto, Yoshiko, Sun, Yuan, Wilson, Richard M, Wojtkiewicz, Gregory, Tricot, Benoit, Osborne, Michael T, Hung, Judy, Vinegoni, Claudio, Naxerova, Kamila, Sosnovik, David E, Zile, Michael R, Bradshaw, Amy D, Liao, Ronglih, Tawakol, Ahmed, Weissleder, Ralph, Rosenzweig, Anthony, Swirski, Filip K, Sam, Flora, Nahrendorf, Matthias
Format: Article
Language:English
Subjects:
Adult
Aged
Aging
Aging - pathology
Aging - physiology
Animals
Bone marrow
Clonal deletion
Collagen
Computed tomography
Diastole - physiology
Female
Fibroblasts
Fibroblasts - pathology
Fibroblasts - physiology
Fibrosis
Heart - physiopathology
Heart diseases
Heart failure
Heart Failure - pathology
Heart Failure - physiopathology
Heart function
Hematopoiesis
Homeostasis
Humans
Hypertension
Hypertension - pathology
Hypertension - physiopathology
Interleukin 10
Interleukin-10 - deficiency
Interleukin-10 - genetics
Interleukin-10 - physiology
Macrophages
Macrophages - pathology
Macrophages - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Monocytes
Monocytes - pathology
Monocytes - physiology
Myeloid cells
Myocardium
Myocardium - pathology
Phenotypes
Positron emission
Positron emission tomography
Rodents
Spleen
Stiffness
Stroke Volume - physiology
Tomography
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen. In humans, we observed a parallel constellation of hematopoietic activation: circulating myeloid cells are more frequent, and splenic F-FDG PET/CT imaging signal correlates with echocardiographic indices of diastolic dysfunction. While diastolic dysfunction develops, cardiac macrophages produce IL-10, activate fibroblasts, and stimulate collagen deposition, leading to impaired myocardial relaxation and increased myocardial stiffness. Deletion of IL-10 in macrophages improves diastolic function. These data imply expansion and phenotypic changes of cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20171274