Validation of the circulating monocyte being representative of the cholesterol-loaded macrophage: Biomediator activity

Sridevi Devaraj, Ishwarlal Jialal

Research output: Contribution to journalArticle

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Abstract

Context. - Inflammation is pivotal to atherosclerosis. The monocyte-macrophage, a crucial cell in atherogenesis, is present during all stages of atherosclerosis. However, there is a paucity of data comparing circulating monocytes to cholesterol-laden macrophages (foam cells), with regard to their atherogenic properties, especially in subjects with established risk factors such as hyperlipidemia. Objective. - To determine whether the circulating blood monocyte is representative of the cholesterol-loaded macrophage with regard to its proatherogenicity in healthy controls and hyperlipidemic patients. Design. - Fasting blood was drawn from 32 subjects (n = 16 controls and n = 16 hyperlipidemic patients), and peripheral blood monocytes were obtained. Also, macrophages were cultured and loaded with acetyl low-density lipoprotein on day 10. Day 1 peripheral blood monocytes and day 11 cholesterol-loaded macrophages were assessed for release of superoxide anion and cytokines (interleukin 1, interleukin 6, tumor necrosis factor α); surface expression of CD11b, VLA-4, and CD40; and adhesion to human endothelium. Results. - Monocyte and cholesterol-loaded macrophage superoxide anion release, cytokines, and adhesion of monocytes to human endothelium were significantly increased in hyperlipidemic patients compared with controls. Furthermore, following cholesterol loading, there were no significant differences in monocyte versus cholesterol-loaded macrophage activity (P = .71). Also, CD14 and CD11b surface expression on monocytes was significantly increased in hyperlipidemic patients as compared with controls. The magnitude of change in the monocytes versus cholesterol-loaded macrophages was similar. Conclusions. - From these studies, we can conclude that the monocyte, which is readily accessible, is an appropriate cell to study for modulation of proatherogenic activity, especially with regard to genomic and proteomic analyses/microarrays.

Original languageEnglish (US)
Pages (from-to)1432-1435
Number of pages4
JournalArchives of Pathology and Laboratory Medicine
Volume132
Issue number9
StatePublished - Sep 2008

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Monocytes
Macrophages
Cholesterol
Atherosclerosis
Superoxides
Endothelium
Cytokines
Integrin alpha4beta1
Foam Cells
Microarray Analysis
Hyperlipidemias
Interleukin-1
Proteomics
Interleukin-6
Fasting
Tumor Necrosis Factor-alpha
Inflammation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Validation of the circulating monocyte being representative of the cholesterol-loaded macrophage : Biomediator activity. / Devaraj, Sridevi; Jialal, Ishwarlal.

In: Archives of Pathology and Laboratory Medicine, Vol. 132, No. 9, 09.2008, p. 1432-1435.

Research output: Contribution to journalArticle

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abstract = "Context. - Inflammation is pivotal to atherosclerosis. The monocyte-macrophage, a crucial cell in atherogenesis, is present during all stages of atherosclerosis. However, there is a paucity of data comparing circulating monocytes to cholesterol-laden macrophages (foam cells), with regard to their atherogenic properties, especially in subjects with established risk factors such as hyperlipidemia. Objective. - To determine whether the circulating blood monocyte is representative of the cholesterol-loaded macrophage with regard to its proatherogenicity in healthy controls and hyperlipidemic patients. Design. - Fasting blood was drawn from 32 subjects (n = 16 controls and n = 16 hyperlipidemic patients), and peripheral blood monocytes were obtained. Also, macrophages were cultured and loaded with acetyl low-density lipoprotein on day 10. Day 1 peripheral blood monocytes and day 11 cholesterol-loaded macrophages were assessed for release of superoxide anion and cytokines (interleukin 1, interleukin 6, tumor necrosis factor α); surface expression of CD11b, VLA-4, and CD40; and adhesion to human endothelium. Results. - Monocyte and cholesterol-loaded macrophage superoxide anion release, cytokines, and adhesion of monocytes to human endothelium were significantly increased in hyperlipidemic patients compared with controls. Furthermore, following cholesterol loading, there were no significant differences in monocyte versus cholesterol-loaded macrophage activity (P = .71). Also, CD14 and CD11b surface expression on monocytes was significantly increased in hyperlipidemic patients as compared with controls. The magnitude of change in the monocytes versus cholesterol-loaded macrophages was similar. Conclusions. - From these studies, we can conclude that the monocyte, which is readily accessible, is an appropriate cell to study for modulation of proatherogenic activity, especially with regard to genomic and proteomic analyses/microarrays.",
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