scholarly journals Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Iryna Voloshyna ◽  
Sangeetha Seshadri ◽  
Kamran Anwar ◽  
Michael J. Littlefield ◽  
Elise Belilos ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Cholesterol Transport ◽  
Tnf Α ◽  
Atp Binding Cassette Transporters ◽  
Modified Lipoproteins ◽  
Control Set ◽  
Necrosis Factor

Tumor necrosis factor- (TNF-)αis a proinflammatory proatherogenic cytokine. Infliximab, an anti-TNF-αmonoclonal antibody, is effective in treating rheumatoid arthritis. However, its impact on cardiovascular burden and lipid transport is unclear. The present study investigates the effect of TNF-αand infliximab on reverse cholesterol transport (RCT) proteins. Uptake of modified lipoproteins by macrophages in the vasculature leads to atherogenic foam cell formation. RCT is mediated by proteins including ATP binding cassette transporters A1 (ABCA1), G1 (ABCG1), liver X receptor- (LXR-)α, and 27-hydroxylase. RCT counteracts lipid overload by ridding cells of excess cholesterol. THP-1 human monocytes were incubated with either TNF-αalone or TNF-αwith infliximab. Expression of proteins involved in cholesterol efflux was analyzed. TNF-αsignificantly reduced both ABCA1 and LXR-αmRNA (to68.5±1.59%,P<0.05, and41.2±0.25%,P<0.01, versus control set as 100%, resp.). Infliximab nullified the TNF-αeffect. Results were confirmed by Western blot. Infliximab abolished the increase in foam cells induced by TNF-α. TNF-αtreatment significantly reduces ABCA1 and LXR-αexpression in monocytes, thus bringing about a proatherogenic state. The anti-TNF drug infliximab, commonly used in rheumatology, restored RCT proteins. This is the first report of an atheroprotective effect of infliximab on RCT in monocytes.

Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy

2020 ◽  
Vol 18 ◽  
Author(s):  
Parimalanandhini Duraisamy ◽  
Sangeetha Ravi ◽  
Mahalakshmi Krishnan ◽  
Catherene M. Livya ◽  
Beulaja Manikandan ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Atherosclerosis Progression ◽  
Proinflammatory Mediators ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Inflammatory Site

: Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

Abstract 43: Cholesterol Efflux Pathways Suppress Inflammasome Activation in Mice and Humans

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Marit Westerterp ◽  
Panagiotis Fotakis ◽  
Mireille Ouimet ◽  
Andrea E Bochem ◽  
Hanrui Zhang ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Inflammasome Activation ◽  
Loss Of Function ◽  
Caspase 1 ◽  
Macrophage Cholesterol Efflux

Plasma high-density-lipoprotein (HDL) has several anti-atherogenic properties, including its key role in functioning as acceptor for ATP-binding cassette A1 and G1 (ABCA1 and ABCG1) mediated cholesterol efflux. We have shown previously that macrophage Abca1/g1 deficiency accelerates atherosclerosis, by enhancing foam cell formation and inflammatory cytokine expression in atherosclerotic plaques. Macrophage cholesterol accumulation activates the inflammasome, leading to caspase-1 cleavage, required for IL-1β and IL-18 secretion. Several studies have suggested that inflammasome activation accelerates atherogenesis. We hypothesized that macrophage Abca1/g1 deficiency activates the inflammasome. In Ldlr -/- mice fed a Western type diet (WTD), macrophage Abca1/g1 deficiency increased IL-1β and IL-18 plasma levels (2-fold; P <0.001), and induced caspase-1 cleavage. Deficiency of the inflammasome components Nlrp3 or caspase-1 in macrophage Abca1/g1 knockouts reversed the increase in plasma IL-18 levels ( P <0.001), indicating these changes were inflammasome dependent. We found that macrophage Abca1/g1 deficiency induced caspase-1 cleavage in splenic CD115 + monocytes and CD11b + macrophages. While mitochondrial ROS production or lysosomal function were not affected, macrophage Abca1/g1 deficiency led to an increased splenic population of monocytes (2.5-fold; P <0.01). Monocytes secrete ATP, and as a result, ATP secretion from total splenic cells was increased (2.5-fold; P <0.01), likely contributing to inflammasome activation. Caspase-1 deficiency decreased atherosclerosis in macrophage Abca1/g1 deficient Ldlr -/- mice fed WTD for 8 weeks (225822 vs 138606 μm 2 ; P <0.05). Of therapeutic interest, one injection of reconstituted HDL (100 mg/kg) in macrophage Abca1/g1 knockouts decreased plasma IL-18 levels ( P <0.05). Tangier disease patients, with a homozygous loss-of-function for ABCA1, showed increased IL-1β and IL-18 plasma levels (3-fold; P <0.001), suggesting that cholesterol efflux pathways also suppress inflammasome activation in humans. These findings suggest that macrophage cholesterol efflux pathways suppress inflammasome activation, possibly contributing to the anti-atherogenic effects of HDL treatment.

Pomegranate peel polyphenols inhibit lipid accumulation and enhance cholesterol efflux in raw264.7 macrophages

2016 ◽  
Vol 7 (7) ◽  
pp. 3201-3210 ◽  
Author(s):  
Shengjuan Zhao ◽  
Jianke Li ◽  
Lifang Wang ◽  
Xiaoxia Wu
Keyword(s):  
Lipid Accumulation ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Pomegranate Peel ◽  
Raw264.7 Macrophages

Pomegranate peel polyphenols hindered ox-LDL-induced raw264.7 foam cell formation, by decreasing CD36 and promoting ABCA1 and LXRα expression.

scholarly journals Adenosine A2Areceptor occupancy stimulates expression of proteins involved in reverse cholesterol transport and inhibits foam cell formation in macrophages

2004 ◽  
Vol 76 (3) ◽  
pp. 727-734 ◽  
Author(s):  
Allison B. Reiss ◽  
Mohammad M. Rahman ◽  
Edwin S. L. Chan ◽  
M. Carmen Montesinos ◽  
Nahel W. Awadallah ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Cholesterol Transport

scholarly journals Monocytes from HIV-infected individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration

AIDS ◽  
2015 ◽  
Vol 29 (12) ◽  
pp. 1445-1457 ◽  
Author(s):  
Anna Maisa ◽  
Anna C. Hearps ◽  
Thomas A. Angelovich ◽  
Candida F. Pereira ◽  
Jingling Zhou ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Transendothelial Migration ◽  
Foam Cell Formation
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