Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease.

Autor: Rohde D; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany.; These authors contributed equally: David Rohde, Katrien Vandoorne., Vandoorne K; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Biomedical Engineering Faculty, Technion-Israel Institute of Technology, Haifa, Israel.; These authors contributed equally: David Rohde, Katrien Vandoorne., Lee IH; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Grune J; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Zhang S; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., McAlpine CS; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Schloss MJ; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Nayar R; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Courties G; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Frodermann V; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Wojtkiewicz G; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Honold L; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Chen Q; Max Planck Institute for Molecular Biomedicine, Muenster, Germany., Schmidt S; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Iwamoto Y; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Sun Y; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Cremer S; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Hoyer FF; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Iborra-Egea O; Institut del Cor Germans Trias i Pujol, Barcelona, Spain., Muñoz-Guijosa C; Institut del Cor Germans Trias i Pujol, Barcelona, Spain., Ji F; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA., Zhou B; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China., Adams RH; Max Planck Institute for Molecular Biomedicine, Muenster, Germany., Wythe JD; Cardiovascular Research Institute, Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA., Hidalgo J; Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Barcelona, Spain., Watanabe H; Institute for Molecular Science of Medicine, Aichi Medical University, Aichi, Japan., Jung Y; Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., van der Laan AM; Heart Center, Department of Cardiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Piek JJ; Heart Center, Department of Cardiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Kfoury Y; Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Désogère PA; Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Vinegoni C; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Dutta P; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Sadreyev RI; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Caravan P; Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Bayes-Genis A; Institut del Cor Germans Trias i Pujol, Barcelona, Spain., Libby P; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Scadden DT; Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Lin CP; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Institute for Molecular Science of Medicine, Aichi Medical University, Aichi, Japan., Naxerova K; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Swirski FK; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Nahrendorf M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2022 Jan; Vol. 1 (1), pp. 28-44. Date of Electronic Publication: 2021 Dec 23.
DOI: 10.1038/s44161-021-00002-8
Abstrakt: Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart. The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ's microvasculature is unknown. Here we show that hypertension, atherosclerosis and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis. Limiting angiogenesis with endothelial deletion of Vegfr2 (encoding vascular endothelial growth factor (VEGF) receptor 2) curbed emergency hematopoiesis after MI. We noted that bone marrow endothelial cells assumed inflammatory transcriptional phenotypes in all examined stages of cardiovascular disease. Endothelial deletion of Il6 or Vcan (encoding versican), genes shown to be highly expressed in mice with atherosclerosis or MI, reduced hematopoiesis and systemic myeloid cell numbers in these conditions. Our findings establish that cardiovascular disease remodels the vascular bone marrow niche, stimulating hematopoiesis and production of inflammatory leukocytes.
Databáze: MEDLINE