| Literature DB >> 31700184 |
Vanessa Frodermann1, David Rohde1, Gabriel Courties1, Nicolas Severe2,3, Maximilian J Schloss1, Hajera Amatullah4, Cameron S McAlpine1, Sebastian Cremer1, Friedrich F Hoyer1, Fei Ji5,6, Ian D van Koeverden7, Fanny Herisson1, Lisa Honold1, Gustavo Santos Masson1, Shuang Zhang1, Jana Grune1, Yoshiko Iwamoto1, Stephen P Schmidt1, Gregory R Wojtkiewicz1, I-Hsiu Lee1, Karin Gustafsson2,3, Gerard Pasterkamp8, Saskia C A de Jager7,9, Ruslan I Sadreyev6,10, Jean MacFadyen11, Peter Libby11, Paul Ridker11, David T Scadden2,3, Kamila Naxerova1, Kate L Jeffrey4, Filip K Swirski1, Matthias Nahrendorf12,13,14.
Abstract
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.Entities:
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Year: 2019 PMID： 31700184 PMCID： PMC6858591 DOI： 10.1038/s41591-019-0633-x
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440