Ceramide-enriched LDL induces cytokine release through TLR4 and CD14 in monocytes. Similarities with electronegative LDL

Estruch, Montserrat; Sánchez-Quesada, José Luís; Ordóñez-Llanos, Jordi; Benı́tez, Sònia

doi:10.1016/j.arteri.2013.12.003

Cited by 14 publications

(12 citation statements)

References 36 publications

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“…While TLR4 was originally described as a pattern receptor that recognizes lipopolysaccharide, endogenous ligands, such as ox-LDL, fibronectin and heat shock protein, are known to be TLR4 activators [35]. Modifications of LDL, icluding ceramide-enriched LDL can induce TLR4 expression [36]. In this study, serum levels of LDL and aortic TLR4 gene expression in the occlusal disharmony were significantly higher than those in the control group.…”

Section: Discussionmentioning

confidence: 56%

Occlusal disharmony accelerates the initiation of atherosclerosis in apoE knockout rats

et al. 2014

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BackgroundPsychosocial stress is one of the risk factors for atherosclerosis. As occlusal disharmony induces psychological stress, we hypothesized that psychological stress by occlusal disharmony accelerates atherosclerosis. The aim of this study was to investigate the effects of occlusal disharmony on the initiation of atherosclerosis in apolipoprotein E (apoE) knockout rats.MethodsFourteen male apoE-knockout rats (age; 8 weeks) (Sprague–Dawley strain background) were divided into two groups of seven rats: the occlusal disharmony group and the no treatment (control) group. In the occlusal disharmony group, the maxillary molar cusps were cut off for the 8-week experimental period.ResultsIn the occlusal disharmony group, the percentages of the area of total aortic lumen occupied by plaques and lipid were significantly higher than those in the control group (p < 0.05, t-test). The occlusal disharmony group also showed significantly higher serum levels of very low-density lipoprotein-cholesterol (VLDL) and low-density lipoprotein-cholesterol (LDL), plasma levels of corticosterone (1.9, 1.3 and 1.3 times, respectively), higher aortic protein expression levels of vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1) (1.5 and 1.4 times, respectively), and higher aortic gene expression of levels of VCAM1 and Toll-like receptor 4 (TLR4) (1.9 and 4.3 times, respectively), as compared to the control group (p < 0.05). However, there were no significant differences in serum levels of oxidized LDL, reactive oxygen metabolites and C-reactive protein between the two groups.ConclusionIn apoE knockout rats, occlusal disharmony may induce VCAM1, ICAM1 and TLR4 expression and accelerate the initiation of atherosclerosis.

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Section: Discussionmentioning

confidence: 56%

Occlusal disharmony accelerates the initiation of atherosclerosis in apoE knockout rats

et al. 2014

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“… 86 Similar cytokine-inducing effect has also been described for the ceramide-enriched LDL, which shares most of the properties of LDL(–). 87 , 88 …”

Section: Ldl Electronegativity Indexmentioning

confidence: 99%

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

Ivanova

Bobryshev

Orekhov³

2015

VHRM

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High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(–)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(–), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk.

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“…Under pathological conditions, macrophage activation leads to the release of inflammatory cytokines in response to several activators, including not only external stimuli but also endogenous signals with damage-associated molecular patterns. Immune response and inflammation are features of all stages in response to LDL(−) [12,25]. The main objectives were to assess the induction of an inflammatory profile and the accumulation of intracellular lipids.…”

Section: Introductionmentioning

confidence: 99%

Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages

Puig

Montolio²,

Camps‐Renom

et al. 2020

Cells

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Electronegative low-density lipoprotein (LDL) (LDL(−)), a modified LDL that is present in blood and exerts atherogenic effects on endothelial cells and monocytes. This study aimed to determine the action of LDL(−) on monocytes differentiated into macrophages. LDL(−) and in vitro-modified LDLs (oxidized, aggregated, and acetylated) were added to macrophages derived from THP1 monocytes over-expressing CD14 (THP1-CD14). Then, cytokine release, cell differentiation, lipid accumulation, and gene expression were measured by ELISA, flow cytometry, thin-layer chromatography, and real-time PCR, respectively. LDL(−) induced more cytokine release in THP1-CD14 macrophages than other modified LDLs. LDL(−) also promoted morphological changes ascribed to differentiated macrophages. The addition of high-density lipoprotein (HDL) and anti-TLR4 counteracted these effects. LDL(−) was highly internalized by macrophages, and it was the major inductor of intracellular lipid accumulation in triglyceride-enriched lipid droplets. In contrast to inflammation, the addition of anti-TLR4 had no effect on lipid accumulation, thus suggesting an uptake pathway alternative to TLR4. In this regard, LDL(−) upregulated the expression of the scavenger receptors CD36 and LOX-1, as well as several genes involved in triglyceride (TG) accumulation. The importance and novelty of the current study is that LDL(−), a physiologically modified LDL, exerted atherogenic effects in macrophages by promoting differentiation, inflammation, and triglyceride-enriched lipid droplets formation in THP1-CD14 macrophages, probably through different receptors.

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Ceramide-enriched LDL induces cytokine release through TLR4 and CD14 in monocytes. Similarities with electronegative LDL

Cited by 14 publications

References 36 publications

Occlusal disharmony accelerates the initiation of atherosclerosis in apoE knockout rats

Occlusal disharmony accelerates the initiation of atherosclerosis in apoE knockout rats

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages

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