Macrophages heterogeneity in atherosclerosis - implications for therapy.
Bottom Line: As well as modulating lipid metabolism, macrophages secrete inflammatory cytokines, chemokines and reactive oxygen and nitrogen species that drive pathogenesis.Pharmacological modulation of macrophage activity therefore represents a potential therapeutic strategy for atherosclerosis.This will present a foundation for highlighting novel opportunities to exploit the heterogeneity of macrophages as important diagnostic and therapeutic targets for atherosclerosis and its associated diseases.
Affiliation: School of Medicine and Dentistry, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK. firstname.lastname@example.orgShow MeSH
Related in: MedlinePlus
Mentions: Macrophage heterogeneity exists in tissue in vivo although the phenotype observed may not directly correspond to simplistic phenotypes generated in vitro. In vivo, macrophages are exposed to a complex microenvironment generated from several cell types. The way infiltrating macrophages are activated is dictated by a multitude of signals impinging on their receptors (see Fig. 1). These signals change during the evolution of the underlying disease process and have the capacity to influence the outcome of the disease. Other less-defined macrophage subtypes induced by metabolic factors are liable to be present in atherosclerotic plaques. For example, uptake of oxidized or acetylated LDL, as a model of foam cell formation increases the expression of commonly used M1 markers and transcription factors such as iNOS, metalloproteinase-1 and NF-κB . Fatty acids present in developing plaques activate an inflammatory programme; saturated fatty acids are robustly pro-inflammatory, polyunstaturated fatty acids are weakly inflammatory or neutral while omega-3 unsaturated fatty acids induce more anti-inflammatory functions . Moreover, under appropriate conditions, infiltrating monocytes differentiate into osteoclast-like cells within plaques and promote lesion calcification , whereas macrophages exposed to particulate calcium mineral have been reported to undergo osteoclastic differentiation .
Affiliation: School of Medicine and Dentistry, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK. email@example.com