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 Pallante; Raimondo Carnevale; Sara Perrotta; Daniela Carnevale; Oriol Iborra-Egea; Christian Muñoz-Guijosa; Carolina Galvez-Monton; Antoni Bayes-Genis; Charles Vidoudez; Sunia A Trauger; David Scadden; Filip K Swirski; Michael A Moskowitz; Kamila Naxerova; Matthias Nahrendorf

doi:10.1038/s44161-023-00388-7

Bone marrow adipocytes fuel emergency hematopoiesis after myocardial infarction

Nat Cardiovasc Res. 2023 Dec;2(12):1277-1290. doi: 10.1038/s44161-023-00388-7. Epub 2023 Dec 5.

Authors

Shuang Zhang^{1

2}, Alexandre Paccalet^{1

2}, David Rohde^{1

2}, Sebastian Cremer^{1

2}, Maarten Hulsmans^{1

2}, I-Hsiu Lee^{1

2}, Kyle Mentkowski^{1

2}, Jana Grune^{1

2}, Maximilian J Schloss^{1

2}, Lisa Honold^{1

2}, Yoshiko Iwamoto¹, Yi Zheng², Miriam A Bredella², Colleen Buckless², Brian Ghoshhajra², Vikas Thondapu², Anja M van der Laan³, Jan J Piek³, Hans W M Niessen⁴, Fabio Pallante⁵, Raimondo Carnevale⁵, Sara Perrotta⁵, Daniela Carnevale^{5

6}, Oriol Iborra-Egea⁷, Christian Muñoz-Guijosa⁷, Carolina Galvez-Monton⁷, Antoni Bayes-Genis⁷, Charles Vidoudez⁸, Sunia A Trauger⁸, David Scadden⁹, Filip K Swirski¹⁰, Michael A Moskowitz^{1

2}, Kamila Naxerova^{1

2}, Matthias Nahrendorf^{1

2

11

12}

Affiliations

¹ Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
² Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³ Department of Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Pathology and Cardiac Surgery, Amsterdam Cardiovascular Sciences, Amsterdam UMC, VU Medical Center, Amsterdam, The Netherlands.
⁵ Department of AngioCardioNeurology and Translational Medicine, I.R.C.C.S. INM Neuromed, Pozzilli, Italy.
⁶ Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
⁷ Institut del Cor Germans Trias i Pujol, Barcelona, Spain.
⁸ Harvard Center for Mass Spectrometry, Harvard University, Cambridge, MA, USA.
⁹ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
¹⁰ Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹² Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.

Abstract

After myocardial infarction (MI), emergency hematopoiesis produces inflammatory myeloid cells that accelerate atherosclerosis and promote heart failure. Since 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 following MI. Inhibiting lipolysis in adipocytes using Adipoq^CreERT2Atgl^fl/fl mice or local depletion of bone marrow adipocytes in Adipoq^CreERT2iDTR 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.

Keywords: Myocardial infarction; adipocytes; bone marrow; emergency hematopoiesis; fatty acid oxidation; lipolysis.

Abstract

Grants and funding