The role of monocytosis and neutrophilia in atherosclerosis

J Cell Mol Med. 2018 Mar;22(3):1366-1382. doi: 10.1111/jcmm.13462. Epub 2018 Jan 24.

Abstract

Monocytosis and neutrophilia are frequent events in atherosclerosis. These phenomena arise from the increased proliferation of hematopoietic stem and multipotential progenitor cells (HSPCs) and HSPC mobilization from the bone marrow to other immune organs and circulation. High cholesterol and inflammatory signals promote HSPC proliferation and preferential differentiation to the myeloid precursors (i.e., myelopoiesis) that than give rise to pro-inflammatory immune cells. These cells accumulate in the plaques thereby enhancing vascular inflammation and contributing to further lesion progression. Studies in animal models of atherosclerosis showed that manipulation with HSPC proliferation and differentiation through the activation of LXR-dependent mechanisms and restoration of cholesterol efflux may have a significant therapeutic potential.

Keywords: atherosclerosis; atherosclerotic plaque; chemokines; inflammation; monocyte; neutrophil.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Cholesterol / immunology*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / immunology*
  • Hypercholesterolemia / pathology
  • Liver X Receptors / genetics
  • Liver X Receptors / immunology
  • Mice
  • Monocytes / immunology*
  • Monocytes / pathology
  • Multipotent Stem Cells / immunology
  • Multipotent Stem Cells / pathology
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / deficiency
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / immunology
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / immunology*
  • Plaque, Atherosclerotic / pathology

Substances

  • Liver X Receptors
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Cholesterol