CD11c/CD18 Signals Very Late Antigen-4 Activation To Initiate Foamy Monocyte Recruitment during the Onset of Hypercholesterolemia

Foster, Gregory D.; Lu, Xu; Chidambaram, Alagu A.; Soderberg, Stephanie R.; Armstrong, Ehrin J.; Wu, Huaizhu; Simon, Scott I.

doi:10.4049/jimmunol.1501077

Cited by 30 publications

(35 citation statements)

References 53 publications

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“…Consistent with previous studies (20), levels of CD11c, a β2 integrin that mediates monocyte adhesion to endothelial cells and contributes to the development of atherosclerosis (15,20,26,27,40), were higher on nonclassical and intermediate monocytes than on classical monocytes within individuals, and a high-fat meal increased CD11c levels on nonclassical, but not classical or intermediate, monocytes in subjects with hypertriglyceridemia (Figures 4A–4C). Compared to pretreatment, treatment with MAT9001 or EPA-EE reduced fasting and postprandial CD11c levels on classical and intermediate monocytes (Figures 4A and 4B), with no significant differences between MAT9001 and EPA-EE treatments.…”

Section: Resultssupporting

confidence: 91%

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Perrard

Lian

Bobotas³

et al. 2017

Journal of Clinical Lipidology

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Background Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 polyunsaturated fatty acids (PUFAs) reduce blood triglyceride levels. Effects of triglyceride-lowering therapy on monocyte phenotypes are not well known. Objective We examined effects of n-3 PUFA treatments (eicosapentaenoic acid [EPA] plus docosapentaenoic acid [DPA] [MAT9001] versus EPA ethyl esters [EPA-EE]) on monocyte phenotypes in individuals with hypertriglyceridemia. Methods Individuals with triglycerides 200–400 mg/dL were recruited. Subjects received two treatments in randomized order for 14 days each: MAT9001 and EPA-EE, at 4 g/day. At 2 days before the start of, and on the last day of, each treatment, nile red staining for lipids and phenotypes of each monocyte subset were examined by flow cytometry after an overnight fast and postprandially after a high-fat meal. Results Treatment with MAT9001 or EPA-EE reduced fasting triglyceride levels and decreased proportions of intermediate monocytes. Only MAT9001 decreased postprandial blood triglyceride levels, lowered fasting nile red levels, indicating less lipid in classical and intermediate monocytes, and reduced postprandial CD11c levels on nonclassical monocytes. MAT9001 and EPA-EE each reduced fasting and postprandial CD11c and CD36 levels on classical and intermediate monocytes and postprandial CCR5 levels on intermediate and nonclassical monocytes, with no significant differences between the two treatments. Conclusions Treatment with MAT9001 in individuals with hypertriglyceridemia reduced fasting nile red staining for lipids in classical and intermediate monocytes. MAT9001 and EPA-EE each improved fasting and postprandial monocyte phenotypes, which could potentially help to protect against atherosclerosis.

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Section: Resultssupporting

confidence: 91%

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Perrard

Lian

Bobotas³

et al. 2017

Journal of Clinical Lipidology

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“…While the role of circulating monocytes as precursors of macrophages, which after moving to the subendothelial space become foam cells, is clearly defined (Moore and Tabas, 2011;Tabas and Bornfeldt, 2016), our previous results support the emerging paradigm that monocytes interacting with proinflammatory products released by endothelial cells may acquire a foamy phenotype well before they cross the endothelial layer and differentiate into macrophages (Wu et al, 2009;Foster et al, 2015;Robbins et al, 2013;Xu et al, 2015). The accumulation of lipid droplets in the monocytes is accompanied by increased expression of adhesion and chemokine receptors and overall proinflammatory markers, resulting in a higher risk of cardiovascular disease.…”

Section: Introductionsupporting

confidence: 76%

“…The accumulation of lipid droplets in the monocytes is accompanied by increased expression of adhesion and chemokine receptors and overall proinflammatory markers, resulting in a higher risk of cardiovascular disease. Thus lipid droplets in circulating monocytes are being considered not only a possible therapeutic target, but also a marker of risk (Wu et al, 2009;Foster et al, 2015;Robbins et al, 2013;Xu et al, 2015). In this regard, our molecular analysis of the fatty acid composition of the neutral lipids of foamy monocytes revealed their selective enrichment in a relatively minor fatty acid, identified as palmitoleic acid (Guijas et al, 2012).…”

Section: Introductionmentioning

confidence: 89%

Foamy Monocytes Are Enriched in cis -7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease

Guijas

Meana

Astudillo

et al. 2016

Cell Chemical Biology

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Human monocytes respond to arachidonic acid, a secretory product of endothelial cells, by activating the de novo pathway of fatty acid biosynthesis, resulting in the acquisition of a foamy phenotype due to accumulation of cytoplasmic lipid droplets. Recruitment of foamy monocytes to endothelium is a key step in the formation of atherosclerotic plaques. Here we describe that lipid droplets of foamy monocytes are enriched in a rather uncommon fatty acid, cis-7-hexadecenoic acid (16:1n-9), a positional isomer of palmitoleic acid. 16:1n-9 was found to possess an anti-inflammatory activity both in vitro and in vivo that is comparable with that of omega-3 fatty acids and clearly distinguishable from the effects of palmitoleic acid. Selective accumulation in neutral lipids of phagocytic cells of an uncommon fatty acid reveals an early phenotypic change that may provide a biomarker of proatherogenicity, and a potential target for intervention in the early stages of cardiovascular disease.

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“…2B, C). This is consistent with the fact that both E-selectin ligands and VLA-4 (α4β1 integrin) are expressed on the monocyte and their binding to endothelial E-selectin and VCAM-1 contribute to monocyte-endothelial cell interaction [35]. 11,12-DHET treatment of HAEC did not alter monocyte recruitment compared to vehicle control (Fig.…”

Section: Resultssupporting

confidence: 85%

11,12-Epoxyecosatrienoic acids mitigate endothelial dysfunction associated with estrogen loss and aging: Role of membrane depolarization

Sun

Simon

Foster

et al. 2016

Journal of Molecular and Cellular Cardiology

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Objective Endothelial dysfunction, including upregulation of inflammatory adhesion molecules and impaired vasodilatation, is a key element in cardiovascular disease. Aging and estrogen withdrawal in women are associated with endothelial inflammation, vascular stiffness and increased cardiovascular disease. Epoxyecosatrienoic acids (EETs), the products of arachidonic acid metabolism mediated by cytochrome P450 (CYP) 2J, 2C and other isoforms, are regulated by soluble epoxide hydrolase (sEH)-catalyzed conversion into less active diols. We hypothesized that 11,12-EETs would reduce the endothelial dysfunction associated with aging and estrogen loss. Approach/results When stabilized by an sEH inhibitor (seHi), 11,12-EET at a physiologically low dose (0.1 nM) reduced cytokine-stimulated upregulation of adhesion molecules on human aorta endothelial cells (HAEC) and monocyte adhesion under shear flow through marked depolarization of the HAEC when combined with TNFα. Mechanistically, neither 11,12-EETs nor 17β-estradiol (E2) at physiologic concentrations prevented activation of NFκB by TNFα. E2 at physiological concentrations reduced sEH expression in HAEC, but did not alter CYP expression, and when combined with TNFα depolarized the cell. We also examined vascular dysfunction in adult and aged ovariectomized Norway brown rats (with and without E2 replacement) using an ex-vivo model to analyze endothelial function in an intact segment of artery. sEHi and 11,12-EET with or without E2 attenuated phenylephrine induced constriction and increased endothelial-dependent dilation of aortic rings from ovariectomized rats. Conclusions Increasing 11,12-EETs through sEH inhibition effectively attenuates inflammation and may provide an effective strategy to preserve endothelial function and prevent atherosclerotic heart disease in postmenopausal women.

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CD11c/CD18 Signals Very Late Antigen-4 Activation To Initiate Foamy Monocyte Recruitment during the Onset of Hypercholesterolemia

Cited by 30 publications

References 53 publications

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Foamy Monocytes Are Enriched in cis -7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease

11,12-Epoxyecosatrienoic acids mitigate endothelial dysfunction associated with estrogen loss and aging: Role of membrane depolarization

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