Claudio Vinegoni, Ph.D. | Cardiac macrophages promote diastolic dysfunction

J. Exp. Med.
Cardiac macrophages promote diastolic dysfunction

Hulsmans, M., Sager, H. B., Roh, J. D., Valero-Munoz, M., Houstis, N. E., Iwamoto, Y., Sun, Y., Wilson, R. M., Wojtkiewicz, G., Tricot, B., Osborne, M. T., Hung, J., Vinegoni, C., Naxerova, K., Sosnovik, D. E., Zile, M. R., Bradshaw, A. D., Liao, R., Tawakol, A., Weissleder, R., Rosenzweig, A., Swirski, F. K., Sam, F., and Nahrendorf^#, M.

Journal of Experimental Medicine 2018

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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-18-FDGPET/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.
@article{2018-JEM, author= {Hulsmans, M. and Sager, H. B. and Roh, J. D. and Valero-Munoz, M. and Houstis, N. E. and Iwamoto, Y. and Sun, Y. and Wilson, R. M. and Wojtkiewicz, G. and Tricot, B. and Osborne, M. T. and Hung, J. and Vinegoni, C. and Naxerova, K. and Sosnovik, D. E. and Zile, M. R. and Bradshaw, A. D. and Liao, R. and Tawakol, A. and Weissleder, R. and Rosenzweig, A. and Swirski, F. K. and Sam, F. and Nahrendorf<sup>#</sup>, M.}, title= {Cardiac macrophages promote diastolic dysfunction}, journal= {Journal of Experimental Medicine}, alternatejournal = {J. Exp. Med.}, year = {2018}, volume = {215}, number = {2}, pages = {423-440}, issn = {0022-1007}, doi = {10.1084/jem.20171274}, pmcid = {PMC3366498}, pmid= {29339450} }
29339450

PMC3366498

10.1084/jem.20171274

Abstract

"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-18-FDGPET/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."

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For attribution in academic contexts, please cite this work as:

Hulsmans, M., Sager, H. B., Roh, J. D., Valero-Munoz, M., Houstis, N. E., Iwamoto, Y., Sun, Y., Wilson, R. M., Wojtkiewicz, G., Tricot, B., Osborne, M. T., Hung, J., Vinegoni, C., Naxerova, K., Sosnovik, D. E., Zile, M. R., Bradshaw, A. D., Liao, R., Tawakol, A., … Nahrendorf^#, M. (2018). Cardiac macrophages promote diastolic dysfunction. Journal of Experimental Medicine, 215(2), 423–440. https://doi.org/10.1084/jem.20171274