TY - JOUR
T1 - Bone marrow adipocytes fuel emergency hematopoiesis after myocardial infarction
AU - Zhang, Shuang
AU - Paccalet, Alexandre
AU - Rohde, David
AU - Cremer, Sebastian
AU - Hulsmans, Maarten
AU - Lee, I. Hsiu
AU - Mentkowski, Kyle
AU - Grune, Jana
AU - Schloss, Maximilian J.
AU - Honold, Lisa
AU - Iwamoto, Yoshiko
AU - Zheng, Yi
AU - Bredella, Miriam A.
AU - Buckless, Colleen
AU - Ghoshhajra, Brian
AU - Thondapu, Vikas
AU - van der Laan, Anja M.
AU - Piek, Jan J.
AU - Niessen, Hans W. M.
AU - Pallante, Fabio
AU - Carnevale, Raimondo
AU - Perrotta, Sara
AU - Carnevale, Daniela
AU - Iborra-Egea, Oriol
AU - Muñoz-Guijosa, Christian
AU - Galvez-Monton, Carolina
AU - Bayes-Genis, Antoni
AU - Vidoudez, Charles
AU - Trauger, Sunia A.
AU - Scadden, David T.
AU - Swirski, Filip K.
AU - Moskowitz, Michael A.
AU - Naxerova, Kamila
AU - Nahrendorf, Matthias
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85178405561&origin=inward
U2 - 10.1038/s44161-023-00388-7
DO - 10.1038/s44161-023-00388-7
M3 - Article
C2 - 38344689
SN - 2731-0590
VL - 2
SP - 1277
EP - 1290
JO - Nature cardiovascular research
JF - Nature cardiovascular research
IS - 12
ER -