Abstract
Atherosclerosis is a chronic inflammatory disease that may ultimately lead to local proteolysis, plaque rupture, and thrombotic vascular disease, resulting in myocardial infarction, stroke, and sudden cardiac death. Circulating monocytes are recruited to the arterial wall in response to inflammatory insults and differentiate into macrophages which make a critical contribution to tissue damage, wound healing, and also regression of atherosclerotic lesions. Within plaques, macrophages take up aggregated lipoproteins which have entered the vessel wall to give rise to cholesterol-engorged foam cells. Also, the macrophage phenotype is influenced by various stimuli which affect their polarization, efferocytosis, proliferation, and apoptosis. The heterogeneity of macrophages in lesions has recently been addressed by single-cell sequencing techniques. This article reviews recent advances regarding the roles of macrophages in different stages of disease pathogenesis from initiation to advanced atherosclerosis. Macrophage-based therapies for atherosclerosis management are also described.
Highlights
Atherosclerosis (AS) is associated with both metabolic dysfunction and chronic inflammatory processes
AS is an inflammation-driven disease and Mφs play a central role in the pathogenesis of AS and controlling inflammation in all stages
Understanding monocytes differentiation into either pro- or anti-inflammatory Mφs within lesions and how Mφs affect plaque initiation and progression is of potential importance for the treatment of AS
Summary
Specialty section: This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology. Atherosclerosis is a chronic inflammatory disease that may lead to local proteolysis, plaque rupture, and thrombotic vascular disease, resulting in myocardial infarction, stroke, and sudden cardiac death. Circulating monocytes are recruited to the arterial wall in response to inflammatory insults and differentiate into macrophages which make a critical contribution to tissue damage, wound healing, and regression of atherosclerotic lesions. Macrophages take up aggregated lipoproteins which have entered the vessel wall to give rise to cholesterol-engorged foam cells. The heterogeneity of macrophages in lesions has recently been addressed by single-cell sequencing techniques. This article reviews recent advances regarding the roles of macrophages in different stages of disease pathogenesis from initiation to advanced atherosclerosis. Macrophage-based therapies for atherosclerosis management are described
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