Details

Autor(en) / Beteiligte

• Frodermann, Vanessa
• Rohde, David
• Courties, Gabriel
• Severe, Nicolas
• Schloss, Maximilian J.
• Amatullah, Hajera
• McAlpine, Cameron S.
• Cremer, Sebastian
• Hoyer, Friedrich F.
• Ji, Fei
• van Koeverden, Ian D.
• Herisson, Fanny
• Honold, Lisa
• Masson, Gustavo Santos
• Zhang, Shuang
• Grune, Jana
• Iwamoto, Yoshiko
• Schmidt, Stephen P.
• Wojtkiewicz, Gregory R.
• Lee, I-Hsiu
• Gustafsson, Karin
• Pasterkamp, Gerard
• de Jager, Saskia C. A.
• Sadreyev, Ruslan I.
• MacFadyen, Jean
• Libby, Peter
• Ridker, Paul
• Scadden, David T.
• Naxerova, Kamila
• Jeffrey, Kate L.
• Swirski, Filip K.
• Nahrendorf, Matthias

Titel

Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells

Ist Teil von

• Nature medicine, 2019-11, Vol.25 (11), p.1761-1771

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 -creER T2 ; Lepr fl/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.