Rosuvastatin Inhibits Interleukin (IL)‐8 and IL‐6 Production in Human Coronary Artery Endothelial Cells Stimulated With <i>Aggregatibacter actinomycetemcomitans</i> Serotype b

Gualtero, Diego; Viafara-García, Sergio M.; Morantes, Sandra Johanna; Buitrago, Diana Marcela; González, Octavio A.; Lafaurie, Gloria Inés

doi:10.1902/jop.2016.160288

Cited by 18 publications

(27 citation statements)

References 52 publications

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“…Of interest, this effect seemed to be mainly driven by IL-6 and IL-8 ( Fig. 2), two of the most studied cytokines in the atherosclerotic process and already associated to the statin related benefit in experiments conducted on coronary artery endothelial cells [29,30]. A similar trend for statin induced IL-6 and Il-8 reduction, although not statistically significant, was found in vivo.…”

Section: Discussionmentioning

confidence: 64%

Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue

Parisi

Petraglia

D’Esposito

et al. 2019

International Journal of Cardiology

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Background: Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation. Methods: Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies. Results: Statin therapy was significantly associated with lower EAT thickness (p b 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p b 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p b 0.0001). Conclusions: The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.

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Section: Discussionmentioning

confidence: 64%

Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue

Parisi

Petraglia

D’Esposito

et al. 2019

International Journal of Cardiology

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“…The chemokines IL-8 and MCP-1 have been reported as key inflammatory chemokines that induce chemotactic and stimulatory responses and promote monocyte and endothelial cell interactions (31,32). Lipopolysaccharide derived from enterobacteria induces the expression of these chemokines in HCAECs; however, in models with periodontopathogens, studies of LPS have been limited to P. gingivalis and A. actinomycetemcomitans (22,33). Our results showed a relevant endothelial inflammatory response, as E. corrodens-LPS mainly increased IL-8 and MCP-1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…The levels of MCP‐1, RANTES, MIP‐1α, IL‐8, and GM‐CSF were measured in culture supernatants from HCAECs stimulated with LPS for 6, 12, 24, or 48 h by flow cytometry using a Human Pro‐inflammatory Chemokine Panel (BioLegend, San Diego, CA, USA) according to the manufacturer's instructions. The minimum detectable concentrations of IL‐8, MCP‐1, RANTES, MIP‐1 α , and GM‐CSF were 1.9, 2.2, 3.6, 2.6, and 2.0 pg ml −1 , respectively . Flow cytometry was performed using the BD Accuri C6 flow cytometer (Becton Dickinson Biosciences, San Jose, CA, USA), and the data were processed using BD Accuri C6 Software (Becton Dickinson Biosciences).…”

Section: Methodsmentioning

confidence: 99%

“…After a 1‐h treatment with LPS, HCAEC monolayers grown in 75‐cm 2 flasks were rinsed and scraped, and the nuclear fraction was isolated using a commercial nuclear protein extraction kit (Cayman Chemical, ‎Ann Arbor, MI, USA). The NF‐ κ B p65 DNA‐binding activity in HCAECs was assessed using an NF‐ κ B transcription factor assay (human p65; Cayman Chemical) according to the manufacturer's instructions, as previously reported . Absorbance was measured at 450 nm using a microplate reader (Infinite 200 PRO, Tecan).…”

Section: Methodsmentioning

confidence: 99%

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Eikenella corrodens lipopolysaccharide stimulates the pro‐atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Viafara-García

Gualtero

Avila-Ceballos

et al. 2018

European J Oral Sciences

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Eikenella corrodens is a gram‐negative bacterium, and although primarily associated with periodontal infections or infective endocarditis, it has been identified in coronary atheromatous plaques. The effect of its lipopolysaccharide (LPS) on human coronary artery endothelial cells (HCAECs) is unknown. Our aim was to examine the mechanism underlying the inflammatory response in HCAECs stimulated with E. corrodens‐LPS and to evaluate monocyte adhesion. Endothelial responses were determined by measuring the levels of chemokines and cytokines using flow cytometry. The surface expression of intercellular adhesion molecule 1 (ICAM‐1) was determined using a cell‐based ELISA, and the adhesion of THP‐1 monocytes to HCAECs was also monitored. The involvement of toll‐like receptors (TLRs) 2 and 4 was examined using TLR‐neutralizing antibodies, and activation of extracellular signal‐regulated kinase (ERK)1/2 and nuclear factor‐kappa B (NF‐κB) p65 were measured by western blotting and ELISA, respectively. Eikenella corrodens‐LPS increased secretion of interleukin‐8 (IL‐8), monocyte chemotactic protein 1 (MCP‐1), and granulocyte–macrophage colony‐stimulating factor (GM‐CSF), and expression of ICAM‐1 on the surface of HCAECs, consistent with the increased adhesion of THP‐1 cells. Moreover, E. corrodens‐LPS interacted with TLR4, a key receptor able to maintain the levels of IL‐8, MCP‐1, and GM‐CSF in HCAECs. Phosphorylation of ERK1/2 and activation of NF‐κB p65 were also increased. The results indicate that E. corrodens‐LPS activates HCAECs through TLR4, ERK, and NF‐κB p65, triggering a pro‐atherosclerotic endothelial response and enhancing monocyte adhesion.

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“…The evidence indicates that the interactions between bacteria and ECs play an important role in the pathogenesis of endothelial dysfunction. However, in vitro studies with EC cultures have shown that Pg‐LPS does not induce strong expression of markers of the inflammatory response, while LPS from Aggregatibacter actinomycetemcomitans (Aa) and Eikenella corrodens does (Erridge, Spickett, & Webb, ; Gualtero et al, ; Ho, Guo, Chunga, Goodwin, & Xie, ; Kebschull, Demmer, & Papapanou, ; Viafara‐Garcia, Gualtero, Avila‐Ceballos, & Lafaurie, ). In these two‐dimensional (2D) models, cultured ECs are not exposed to the components of the basement membrane that underlie the endothelium.…”

Section: Introductionmentioning

confidence: 99%

Differential responses of endothelial cells on three‐dimensional scaffolds to lipopolysaccharides from periodontopathogens

Gualtero

Lafaurie

Fontanilla

2019

Molecular Oral Microbiology

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Studies have been conducted on the pathogenicity of periodontopathogens in cultures of endothelial cells on two‐dimensional (2D) polystyrene surfaces, where the monolayer formed is not exposed to proteins of the subendothelial matrix. In this work, we developed a culture system by seeding human coronary artery endothelial cells (HCAECs) onto three‐dimensional (3D) scaffolds of collagen type I, a subendothelial protein. The inflammatory responses of the HCAEC monolayers, formed either on 3D scaffolds or directly on a 2D polystyrene plate, to lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) were evaluated. The transcription of 3 genes, the secretion of 40 cytokines and 2 prostanoids, and the adhesion of monocytes to 2D and 3D cultures with or without exposure to lipopolysaccharides (control) were assessed. HCAECs exhibited differences in transcriptional and secretory profiles between the 3D and 2D models. In addition, the inflammatory responses of HCAEC to Aa‐LPS and Pg‐LPS differed between the two models. In 3D cultures treated with Aa‐LPS, the levels of IL‐8, RANTES, G‐CSF, ICAM‐1, IL‐6, and TXA2 were significantly higher than those in the controls. In 2D cultures treated with Aa‐LPS, IL‐8, RANTES, G‐CSF, ICAM‐1, TNF‐RI, PGI2, and TXA2 levels were significantly higher than those in their controls. In the presence of Aa‐LPS, monocyte adhesion did not differ between treated and control 3D cultures but was significantly higher in treated 2D cultures than in the controls. In response to Pg‐LPS, cytokine‐prostaglandin secretion and monocyte adhesion did not differ between 3D and 2D cultures. These data indicate that HCAECs respond differently to these two types of LPS.

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Rosuvastatin Inhibits Interleukin (IL)‐8 and IL‐6 Production in Human Coronary Artery Endothelial Cells Stimulated With Aggregatibacter actinomycetemcomitans Serotype b

Abstract: These results suggest Aa-induced proinflammatory endothelial responses are regulated by rosuvastatin in a mechanism that appears to involve KLF2 activation. Use of rosuvastatin to prevent cardiovascular disease may reduce risk of endothelial activation by bacterial antigens.

Cited by 18 publications

References 52 publications

Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue

Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue

Eikenella corrodens lipopolysaccharide stimulates the pro‐atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Differential responses of endothelial cells on three‐dimensional scaffolds to lipopolysaccharides from periodontopathogens

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