Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells
Autor: | Kamila Naxerova, Hajera Amatullah, Vanessa Frodermann, Gerard Pasterkamp, I-Hsiu Lee, Fanny Herisson, Nicolas Severe, David Rohde, Gregory R. Wojtkiewicz, Paul M. Ridker, Jana Grune, Friedrich Felix Hoyer, Matthias Nahrendorf, Saskia C. A. de Jager, Yoshiko Iwamoto, Karin Gustafsson, Peter Libby, Lisa Honold, Sebastian Cremer, Gustavo Santos Masson, Ruslan I. Sadreyev, Shuang Zhang, Kate L. Jeffrey, Filip K. Swirski, Gabriel Courties, Fei Ji, Cameron S. McAlpine, Stephen P. Schmidt, Maximilian J. Schloss, Jean G. MacFadyen, Ian D. van Koeverden, David T. Scadden |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Stromal cell Leukocytosis Adipose tissue Inflammation Biochemistry General Biochemistry Genetics and Molecular Biology Epigenome Mice 03 medical and health sciences 0302 clinical medicine Physical Conditioning Animal Leukocytes Animals Humans Medicine Progenitor cell Exercise Homeodomain Proteins Leptin receptor Biochemistry Genetics and Molecular Biology(all) business.industry Leptin General Medicine Atherosclerosis Hematopoietic Stem Cells Hematopoiesis 030104 developmental biology medicine.anatomical_structure Adipose Tissue Cardiovascular Diseases 030220 oncology & carcinogenesis Immunology Receptors Leptin Bone marrow Sedentary Behavior medicine.symptom Transcriptome business Genetics and Molecular Biology(all) |
Zdroj: | Nature Medicine, 25(11), 1761. Nature Publishing Group Nature Medicine |
ISSN: | 1546-170X 1078-8956 |
Popis: | A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creERT2; Leprfl/fl mice reveals that leptin’s effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes. The beneficial effects of exercise on cardiovascular disease are linked to decreased inflammation through crosstalk between adipose tissue and hematopoietic progenitor cells in the bone marrow. |
Databáze: | OpenAIRE |
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