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.
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Atherosclerosis / genetics
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Atherosclerosis / immunology*
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Atherosclerosis / pathology
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Bone Marrow / immunology
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Bone Marrow / pathology
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Cell Differentiation
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Cell Proliferation
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Cholesterol / immunology*
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Disease Models, Animal
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Gene Expression Regulation
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Hematopoietic Stem Cells / immunology
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Hematopoietic Stem Cells / pathology
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Humans
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Hypercholesterolemia / genetics
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Hypercholesterolemia / immunology*
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Hypercholesterolemia / pathology
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Liver X Receptors / genetics
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Liver X Receptors / immunology
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Mice
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Monocytes / immunology*
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Monocytes / pathology
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Multipotent Stem Cells / immunology
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Multipotent Stem Cells / pathology
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Neutrophils / immunology*
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Neutrophils / pathology
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Nuclear Receptor Subfamily 4, Group A, Member 1 / deficiency
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Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
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Nuclear Receptor Subfamily 4, Group A, Member 1 / immunology
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Plaque, Atherosclerotic / genetics
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Plaque, Atherosclerotic / immunology*
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Plaque, Atherosclerotic / pathology
Substances
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Liver X Receptors
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Nr4a1 protein, mouse
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Cholesterol