CD14 and TLR4 mediate cytokine release promoted by electronegative LDL in monocytes

Estruch, Montserrat; Bancells, Cristina; Beloki, Lorea; Sánchez-Quesada, José Luis; Ordóñez-Llanos, Jordi; Benı́tez, Sònia

doi:10.1016/j.atherosclerosis.2013.05.011

Cited by 63 publications

(65 citation statements)

References 30 publications

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“…When the TLR4 receptor is engaged, it activates innate immune cells and is particularly responsive to lipopolysaccharide. In murine models, TLR4 antagonist inhibited vascular inflammation and atherogenesis (Lu, Zhang, Li, Jin, and Huang, 2013), and in human monocytes, Estruch and coworkers (Estruch, Bancells, Beloki, Sanchez-Quesada, Ordonez-Llanos, and Benitez, 2013) discovered that TLR4-mediated inflammatory activation was induced by LDL. Simpson and coworkers (Simpson et al , 2009) showed that an acute bout of aerobic exercise causes changes in TLR expression within specific blood monocyte subpopulations and suggested that the mechanism might be occurring at the cellular level, a speculation that is consistent with our observed changes in monocyte gene expression.…”

Section: Discussionmentioning

confidence: 99%

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Radom‐Aizik

Zaldivar

Haddad

et al. 2014

Brain, Behavior, and Immunity

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Physical activity can prevent and/or attenuate atherosclerosis, a disease clearly linked to inflammation. Paradoxically, even brief exercise induces a stress response and increases inflammatory cells like monocytes in the circulation. We hypothesized that exercise would regulate the expression of genes, gene pathways, and microRNAs in monocytes in a way that could limit pro-inflammatory function and drive monocytes to prevent, rather than contribute to, atherosclerosis. Twelve healthy men (22-30 yr old) performed ten 2-min bouts of cycle ergometer exercise at a constant work equivalent to an average of 82% of maximum O2 consumption interspersed with 1-min rest. Blood was drawn before and immediately after the exercise. Monocytes were isolated from peripheral blood mononuclear cells. Flow cytometry was used to identify monocyte subtypes. We used Affymetrix U133+2.0 arrays for gene expression and Agilent Human miRNA V2 Microarray for miRNAs. A stringent statistical approach (FDR < 0.05) was used to determine that exercise significantly altered the expression of 894 annotated genes and 19 miRNAs. We found distinct gene alterations that were likely to direct monocytes in an anti-inflammatory, anti-atherogenic pathway, including the downregulation of monocyte TNF, TLR4, and CD36 genes and the upregulation of EREG and CXCR4. Exercise significantly altered a number of microRNAs that likely influence monocytes involvement in vascular health. Exercise leads to a novel genomic profile of circulating monocytes, which appears to promote cardiovascular health despite the overall stress response.

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Section: Discussionmentioning

confidence: 99%

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Radom‐Aizik

Zaldivar

Haddad

et al. 2014

Brain, Behavior, and Immunity

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“…It is known that native LDL does not cause accumulation of intracellular lipids but chemically modified LDL is atherogenic causing accumulation of lipids in arterial cells and transforming them into foam cells [28–30]. In the blood of atherosclerotic patients 3 types of atherogenic modified LDL were found, namely, small dense [31], electronegative [32], and desialylated [33] LDLs. All types of atherogenic LDL modification are characterized by the formation of lipoprotein self-associates [34].…”

Section: Discussionmentioning

confidence: 99%

Approach to Reduction of Blood Atherogenicity

Orekhov

Melnichenko

Sobenin

2014

Oxidative Medicine and Cellular Longevity

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We have earlier found that blood sera of patients with coronary heart disease (CHD) increase lipid levels in cells cultured from subendothelial intima of human aorta. We have also revealed that the ability of blood sera to raise intracellular cholesterol; that is, their atherogenicity is caused by at least modified low density lipoprotein (LDL) circulating in the blood of patients and autoantibodies to modified LDL. In the present work we have demonstrated significant impact of nonlipid factor(s) to blood atherogenicity. We have developed an approach to removal of nonlipid atherogenicity factor(s) from blood serum based on the use of immobilized LDL. This approach was used for extracorporeal perfusion of patient's blood through the column with immobilized LDL. Pilot clinical study confirmed the efficacy of this approach for prevention of coronary atherosclerosis progression.

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“…TLRs have a number of co-receptors, of which CD14 is of particular interest since it interacts with several of the TLRs, including TLR2, TLR3, TLR4, TLR6, TLR7, and TLR9 [76]. Recently it was demonstrated that modified LDL induces cytokine release, mediated by TLR4 and CD14, indicating possible therapeutic potential [77].…”

Section: Toll-like Receptorsmentioning

confidence: 98%

The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis

et al. 2015

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Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis.

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CD14 and TLR4 mediate cytokine release promoted by electronegative LDL in monocytes

Cited by 63 publications

References 30 publications

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Approach to Reduction of Blood Atherogenicity

The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis

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