Karina Di Gregoli1, Jason L Johnson. 1. Laboratory of Cardiovascular Pathology, School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, UK.
Abstract
PURPOSE OF REVIEW: The varied effects of colony-stimulating factors (CSFs) on monocytes and macrophages during inflammation and atherosclerosis and its clinical presentation prompt the question whether the differing effects of CSFs dictate macrophage function and disease progression. RECENT FINDINGS: CSFs can give rise to heterogeneous populations of monocyte-derived macrophages that are characterized by disparate expression of distinct molecules which dictate their ability to process lipid and regulate inflammatory and immune responses. The CSFs have been found within atherosclerotic plaques and in the circulation where their levels may act as predictive biomarkers of disease progression. Accordingly, differing exposure to these factors imparts divergent genomic signatures and functional properties on macrophages and may impact the multifactorial steps involved in atherogenesis, plaque progression and instability. SUMMARY: Great interest in macrophage heterogeneity in the genesis and progression of atherosclerosis has led to the search for consistent markers of specific subsets in both animal models and humans. A better understanding of the overlap and competition between CSF regulation of macrophage phenotypes is therefore warranted, to allow their characterization in plaques. Subsequent targeted genetic and pharmacological intervention will facilitate the generation of therapeutic approaches to halt the progression and rupture of advanced atherosclerotic plaques.
PURPOSE OF REVIEW: The varied effects of colony-stimulating factors (CSFs) on monocytes and macrophages during inflammation and atherosclerosis and its clinical presentation prompt the question whether the differing effects of CSFs dictate macrophage function and disease progression. RECENT FINDINGS: CSFs can give rise to heterogeneous populations of monocyte-derived macrophages that are characterized by disparate expression of distinct molecules which dictate their ability to process lipid and regulate inflammatory and immune responses. The CSFs have been found within atherosclerotic plaques and in the circulation where their levels may act as predictive biomarkers of disease progression. Accordingly, differing exposure to these factors imparts divergent genomic signatures and functional properties on macrophages and may impact the multifactorial steps involved in atherogenesis, plaque progression and instability. SUMMARY: Great interest in macrophage heterogeneity in the genesis and progression of atherosclerosis has led to the search for consistent markers of specific subsets in both animal models and humans. A better understanding of the overlap and competition between CSF regulation of macrophage phenotypes is therefore warranted, to allow their characterization in plaques. Subsequent targeted genetic and pharmacological intervention will facilitate the generation of therapeutic approaches to halt the progression and rupture of advanced atherosclerotic plaques.
Authors: Claire Q F Wang; Mayte Suárez-Fariñas; Kristine E Nograles; Claudia A Mimoso; David Shrom; Ernst R Dow; Michael P Heffernan; Robert W Hoffman; James G Krueger Journal: J Invest Dermatol Date: 2014-07-07 Impact factor: 8.551