Bone marrow adipocytes fuel emergency hematopoiesis after myocardial infarction

Shuang Zhang, Alexandre Paccalet, David Rohde, Sebastian Cremer, Maarten Hulsmans, I. Hsiu Lee, Kyle Mentkowski, Jana Grune, Maximilian J. Schloss, Lisa Honold, Yoshiko Iwamoto, Yi Zheng, Miriam A. Bredella, Colleen Buckless, Brian Ghoshhajra, Vikas Thondapu, Anja M. van der Laan, Jan J. Piek, Hans W.M. Niessen, Fabio PallanteRaimondo Carnevale, Sara Perrotta, Daniela Carnevale, Oriol Iborra-Egea, Christian Muñoz-Guijosa, Carolina Galvez-Monton, Antoni Bayes-Genis, Charles Vidoudez, Sunia A. Trauger, David T. Scadden, Filip K. Swirski, Michael A. Moskowitz, Kamila Naxerova, Matthias Nahrendorf

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

After myocardial infarction (MI), emergency hematopoiesis produces inflammatory myeloid cells that accelerate atherosclerosis and promote heart failure. Because the balance between glycolysis and mitochondrial metabolism regulates hematopoietic stem cell homeostasis, metabolic cues may influence emergency myelopoiesis. Here we show, in humans and female mice, that hematopoietic progenitor cells increase fatty acid metabolism after MI. Blockade of fatty acid oxidation by deleting carnitine palmitoyltransferase (Cpt1a) in hematopoietic cells of Vav1 Cre/+ Cpt1a fl/fl mice limited hematopoietic progenitor proliferation and myeloid cell expansion after MI. We also observed reduced bone marrow adiposity in humans, pigs and mice after MI. Inhibiting lipolysis in adipocytes using Adipoq CreERT2 Atgl fl/fl mice or local depletion of bone marrow adipocytes in Adipoq CreERT 2 iDTR mice also curbed emergency hematopoiesis. Furthermore, systemic and regional sympathectomy prevented bone marrow adipocyte shrinkage after MI. These data establish a critical role for fatty acid metabolism in post-MI emergency hematopoiesis.

Original languageEnglish
Pages (from-to)1277-1290
Number of pages14
JournalNature Cardiovascular Research
Volume2
Issue number12
DOIs
StatePublished - Dec 2023

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