Cardiac macrophages promote diastolic dysfunction

J Exp Med. 2018 Feb 5;215(2):423-440. doi: 10.1084/jem.20171274. Epub 2018 Jan 16.


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 18F-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / pathology
  • Aging / physiology
  • Animals
  • Diastole / physiology*
  • Female
  • Fibroblasts / pathology
  • Fibroblasts / physiology
  • Heart / physiopathology*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Hematopoiesis
  • Homeostasis
  • Humans
  • Hypertension / pathology
  • Hypertension / physiopathology
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology
  • Macrophages / pathology*
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Monocytes / pathology
  • Monocytes / physiology
  • Myocardium / pathology*
  • Stroke Volume / physiology


  • IL10 protein, mouse
  • Interleukin-10