In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
Abstract:
Introduction: Elevated cholesterol levels and increased accumulation of myeloid cells are key risk factors in the development of atherosclerosis. Whilst there is significant understanding of the impact of hypercholesterolemia on monocyte function, less is known about the impact of cholesterol on neutrophils. Neutrophils contain the necessary machinery to take up, synthesize, efflux and esterify cholesterol and unique neutrophil phenotypes have been shown in various pathologies, including low density neutrophils (LDNs) described in inflammatory diseases. Aim: Determine if cholesterol loading of neutrophils occurs in hypercholesterolemia and characterize the associated phenotypic and functional consequences. Methods: Patients (n=13) were a mix of familial hypercholesterolemia and mixed dyslipidemia all with total cholesterol 〉 7.0 mmol/L. Age and sex matched healthy donors were used as controls. Normal and low density neutrophils were isolated using a percoll density protocol and further purified by FACS selecting for CD66b + CD15 + cells. Results: LDNs were only present in hypercholesterolemic patients, accounting for 12.29.6% of the cells in the lower density percoll fraction (p 〈 0.01 vs control). LDNs were morphologically similar to mature high density neutrophils and stained positive for neutral lipid. Functionally, LDNs secreted significantly more extracellular traps (NETs) in response to PMA treatment relative to normal density neutrophils isolated from the same patients or healthy controls (p 〈 0.005). Cholesterol loaded neutrophils were more adhesive to endothelial cells compared to controls (p 〈 0.005). Increased NETosis and neutrophil adhesion have been demonstrated to be atherogenic. Phagocytosis was increased in LDNs vs controls (p 〈 0.05). These functional changes could all be replicated in vitro via treatment of neutrophils from healthy subjects with cholesterol or oxLDL. Conclusion: Hypercholesterolemia results in cholesterol loading and a pro-atherosclerotic phenotype in neutrophils. Our data provides evidence that this cholesterol loading occurs in the circulation. More work is now being carried out to further characterize the phenotype of LDNs and mechanisms of maturation during hypercholesterolemia.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.38.suppl_1.609
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
1494427-3
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