Cardiac macrophages promote diastolic dysfunction

Abstract

Hulsmans et al. show that cardiac macrophages expand in left ventricular diastolic dysfunction, a hallmark of heart failure with preserved ejection fraction (HFpEF) and cardiac aging. In HFpEF, macrophages shift toward a profibrotic subset that promotes ventricular stiffness.

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

“…The resulting increase in LV collagen content is a major contributor to the increase in passive myocardial fibre stiffness, which eventually leads to diastolic dysfunction and HFpEF. Importantly, it has been recently shown that the number of macrophages in the heart increase both in animal models and in humans with HFpEF (Hulsmans et al., ). Collectively, these data indicate that macrophages and their secreted proteins play a central role in cardiomyocyte hypertrophy and HFpEF progression (Frantz et al., ).…”

“…In another study, IL‐18 mediated cardiac hypertrophy in rabbits with pressure overload (Yoshida et al., ). Moreover, recent studies in murine models of HFpEF and humans with the disease identified osteopontin as an important mediator in the interaction between macrophages and fibroblasts, where macrophages activate the proliferation of myofibroblasts and production of collagen, which then leads to fibrosis‐mediated cardiac stiffness and eventually HFpEF (Hulsmans et al., ). In addition, IL‐11 is a crucial determinant of cardiac fibrosis (Schafer et al., ).…”

Specialized functions of resident macrophages in brain and heart

“…In addition, expression of these genes by cTM increases with age, particularly at the epicardium, suggests that cTM‐mediated ECM remodelling influences cardiac ageing . Accordingly, cTM have been found to affect diastolic function of the heart by controlling extracellular matrix deposition by fibroblasts . These evidences, as with microglia, suggest trophic roles for cTM in heart homeostasis and highlight a potential role for these resident cells in many more cardiac processes than previously anticipated.…”

“…cTM also contribute to cardiac fibrosis, a hallmark of cardiac senescence that increases with age . cTM secrete a number of pro‐fibrotic factors such as Retnla , Ccl24 , osteopontin, and Tgf1b that may induce fibroblast proliferation and collagen deposition by both TGF‐β‐dependent and ‐independent pathways . In addition, expression of these genes by cTM increases with age, particularly at the epicardium, suggests that cTM‐mediated ECM remodelling influences cardiac ageing .…”

“…Myeloid cell replacement (embryonic vs. adult) and inflammation or aging‐mediated myeloid cell infiltration could therefore have an impact on the heterogeneity and functioning of cTM and microglia and, by extension, on tissue homeostasis. The role of cTM on modulating electrical heart conduction and the association of monocyte‐derived macrophages with fibrotic deposition and diastolic dysfunction prompt redefinition of the contribution of immune cells to idiopathic cardiomyopathies, and might direct generation of novel therapeutics tailored to this organ. Along the same line, phenotypic changes in microglia during age and disease, as well as the contribution of brain‐engrafted macrophages to CNS homeostasis could unveil novel therapeutic approaches to fight neurodegeneration.…”