Deficiency of the NR4A orphan nuclear receptor nor1 in hematopoietic stem cells accelerates atherosclerosis

Hua Qing, Yi Liu, Yue Zhao, Jun Aono, Karrie L. Jones, Elizabeth B. Heywood, Deborah Howatt, Cassi M. Binkley, Alan Daugherty, Ying Liang, Dennis Bruemmer

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The NR4A orphan nuclear receptor NOR1 functions as a constitutively active transcription factor regulating cellular inflammation and proliferation. In this study, we used bone marrow transplantation to determine the selective contribution of NOR1 expression in hematopoietic stem cells to the development of atherosclerosis. Reconstitution of lethally irradiated apoE-/- mice with NOR1-deficient hematopoietic stem cells accelerated atherosclerosis formation and macrophage recruitment following feeding a diet enriched in saturated fat. NOR1 deficiency in hematopoietic stem cells induced splenomegaly and monocytosis, specifically the abundance of inflammatory Ly6C+ monocytes. Bone marrow transplantation studies further confirmed that NOR1 suppresses the proliferation of macrophage and dendritic progenitor (MDP) cells. Expression analysis identified RUNX1, a critical regulator of hematopoietic stem cell expansion, as a target gene suppressed by NOR1 in MDP cells. Finally, in addition to inducing Ly6C+ monocytosis, NOR1 deletion increased the replicative rate of lesional macrophages and induced local foam cell formation within the atherosclerotic plaque. Collectively, our studies demonstrate that NOR1 deletion in hematopoietic stem cells accelerates atherosclerosis formation by promoting myelopoiesis in the stem cell compartment and by inducing local proatherogenic activities in the macrophage, including lesional macrophage proliferation and foam cell formation. Stem Cells 2014;32:2419-2429

Original languageEnglish
Pages (from-to)2419-2429
Number of pages11
JournalStem Cells
Issue number9
StatePublished - Sep 2014


  • Atherosclerosis
  • Macrophage and dendritic progenitors
  • Monocyte
  • Nuclear receptor

ASJC Scopus subject areas

  • General Medicine


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