scholarly journals Changes in the Biomarkers of Oxidative/Nitrosative Stress and Endothelial Dysfunction Are Associated with Cardiovascular Risk in Periodontitis Patients

2021 ◽  
Vol 43 (2) ◽  
pp. 704-715
Author(s):  
Nadia Ferlazzo ◽  
Monica Currò ◽  
Gaetano Isola ◽  
Silvia Maggio ◽  
Maria Paola Bertuccio ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Levels ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Shared Risk

Patients with cardiovascular disease (CVD) and periodontitis (PT) show shared risk factors as result of the altered molecular mechanisms associated with pathological conditions. The aim of our study was to evaluate if the plasma biomarkers associated with endothelial dysfunction may also be related to alterations in the inflammatory status in peripheral blood mononuclear cells (PBMC). Patients with PT, coronary heart disease (CHD), or both diseases as well as controls were enrolled. Plasma levels of coenzyme Q10 (CoQ10), 3-nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) were assessed using HPLC. mRNA levels of caspase-1 (CASP1), NLR family pyrin domain containing 3 (NLRP3), and tumor necrosis factor-α (TNF-α) in PBMC from the recruited subjects were quantified using real-time PCR. Patients with PT + CHD showed lower CoQ10 plasma levels and increased concentrations of NT in comparison to healthy subjects. ADMA levels were higher in CHD and PT + CHD patients compared to controls. Transcript levels of CASP1, NLRP3, and TNF-α were up-regulated in PBMC from all patient groups when compared to healthy subjects. Our results suggest a possible causal link between oxidative stress, high levels of NT and ADMA, and inflammasome activation, which may be involved in the endothelial inflammatory dysfunction leading to the pathogenesis and progression of CHD in PT patients.

scholarly journals Transglutaminase 2 Up-Regulation Is Associated with Inflammatory Response in PBMC from Healthy Subjects with Hypovitaminosis D

2018 ◽  
Vol 6 (4) ◽  
pp. 103 ◽  
Author(s):  
Daniela Caccamo ◽  
Nadia Ferlazzo ◽  
Monica Currò ◽  
Sergio Ricca ◽  
Riccardo Ientile
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Transglutaminase 2 ◽  
Hypovitaminosis D ◽  
Mrna Levels ◽  
Vitamin D Status ◽  
Vitamin D Levels ◽  
Tnf Α

Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires an optimal vitamin D status, we aimed to assess the involvement of TG2/NF-κB signaling in cytokine production in PBMC isolated from adult subjects with different vitamin D status. We observed TG2 up-regulation and a significant positive correlation between TG2 expression and tumor necrosis factor (TNF)-α mRNA levels in PBMC of recruited patients. The mRNA levels of TG2 and TNF-α were higher in PBMC of subjects having hypovitaminosis D, namely plasma 25(OH)vitamin D3 levels lower than 50 nmol/L, than in those with normal vitamin D levels. Moreover, NF-κB up-regulation and nuclear translocation were detected, concomitantly with TG2 as well as TNF-α increased expression, in PBMC of vitamin D-deficient subjects. The present findings confirm that an increase in TG2 expression exacerbates the activation of NF-κB and the production of pro-inflammatory cytokines, and suggest a link between vitamin D deficiency, TG2 up-regulation, and inflammation.

scholarly journals TheBDKRB2 +9/-9 Polymorphisms Influence Pro-Inflammatory Cytokine Levels in Knee Osteoarthritis by Altering TLR-2 Expression: Clinical and in Vitro Studies

2016 ◽  
Vol 38 (3) ◽  
pp. 1245-1256 ◽  
Author(s):  
Shuo Chen ◽  
Lei Zhang ◽  
Ruonan Xu ◽  
Yunfan Ti ◽  
Yunlong Zhao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Knee Oa ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Underlying Mechanisms

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression.

scholarly journals Circulating Anti-Beta2-Glycoprotein I Antibodies Are Associated with Endothelial Dysfunction, Inflammation, and High Nitrite Plasma Levels in Patients with Intermittent Claudication

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Cesar Varela ◽  
Joaquin de Haro ◽  
Silvia Bleda ◽  
Leticia Esparza ◽  
Ignacio Lopez de Maturana ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Intermittent Claudication ◽  
Plasma Levels ◽  
Arterial Disease ◽  
Control Group ◽  
Translational Study ◽  
Reactive Protein ◽  
Glycoprotein I ◽  
Inflammatory Status ◽  
Peripheral Arterial

Our aim is to investigate a possible association of circulating anti-beta2-glycoprotein I antibodies (ABGPI) with the endothelial dysfunction, nitric oxide bioactivity dysregulation, and the inflammatory status that surrounds peripheral arterial disease. We carried out an observational translational study, including 50 male patients with intermittent claudication and a healthy control group of 10 male subjects, age and sex matched with the cases. Flow-mediated arterial dilatation (FMAD) was assessed as a surrogate of endothelial dysfunction, and C-reactive protein (hsCRP) was determined as a marker of inflammation. Nitrite plasma levels were measured by colorimetric analysis. Circulating ABGPI titer was detected with indirect immunofluorescence. Titers <1 : 10 represented the reference range and the lower detection limit of the test. Circulating ABGPI titer ≥1 : 10 was detected in 21 (42%) patients and in none of the control subjects (P<0.01). Patients with ABGPI titer ≥1 : 10 had a lower FMAD (P=0.01). The CRP levels were higher in patients with ABGPI titer ≥1 : 10 (P=0.04). The nitrite plasma levels were higher in patients with ABGPI titer ≥1 : 10 (P<0.01). These data suggest that these circulating ABGPI may collaborate in the development of atherosclerosis; however, further prospective studies are required to establish a causal relationship.

Soluble levels and endogenous vascular gene expression of KLOTHO are related to inflammation in human atherosclerotic disease

2017 ◽  
Vol 131 (21) ◽  
pp. 2601-2609 ◽  
Author(s):  
Ernesto Martín-Núñez ◽  
Javier Donate-Correa ◽  
Ángel López-Castillo ◽  
Alejandro Delgado-Molinos ◽  
Carla Ferri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Serum Levels ◽  
Atherosclerotic Disease ◽  
Inflammatory Disorder ◽  
Mrna Levels ◽  
Atherosclerotic Vascular Disease ◽  
Chronic Inflammatory Disorder ◽  
Control Subjects ◽  
Inflammatory Status ◽  
Tnf Α

Atherosclerosis is a chronic inflammatory disorder affecting the artery wall. Klotho, an anti-aging factor expressed in the vessel walls that participates in the maintenance of vascular homeostasis, can be down-regulated by inflammation. In this proof-of-concept work we seek to characterize the arterial KLOTHO expression in the vascular wall, as well as the serum concentration of this protein, in a group of patients with clinical atherosclerotic disease. In addition, we aim to analyze the relationship between Klotho and inflammation. Vascular samples were obtained from 27 patients with atherosclerotic disease under an elective vascular surgery procedure, and from 11 control subjects (cadaveric organ donation programme). qRT-PCR was performed to analyze the gene expression of KLOTHO, TNF-α, IL-6, and IL-10. Serum levels of soluble KLOTHO were measured by ELISA. As compared with control subjects, serum concentrations and vascular expression of Klotho were lower in patients with atherosclerotic vascular disease, whereas inflammatory status was significantly higher. There was a negative and significant correlation between inflammatory parameters and Klotho. After controlling for the effect of other variables, partial correlation showed a direct relationship between vascular KLOTHO gene expression and IL-10 mRNA levels, whereas there was a negative association with serum LDL concentrations and vascular TNF-α expression. Our study indicates an inverse interrelationship between inflammation and Klotho in atherosclerosis. Further studies are necessary to elucidate whether the inflammatory state causes Klotho deficiency or, on the contrary, reduction of Klotho could be responsible for greater inflammation, and finally, to investigate the potential clinical relevance of this association.

Tissue factor messenger RNA levels in leukocytes compared with tissue factor antigens in plasma from patients in hypercoagulable state caused by various diseases

2004 ◽  
Vol 92 (07) ◽  
pp. 132-139 ◽  
Author(s):  
Tomohiro Sase ◽  
Yuko Kamikura ◽  
Toshihiro Kaneko ◽  
Yasunori Abe ◽  
Junji Nishioka ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Levels ◽  
Messenger Rna ◽  
Healthy Subjects ◽  
Flow Cytometric Analysis ◽  
Antigen Expression ◽  
Normal Subjects ◽  
Hypercoagulable State ◽  
Mrna Levels ◽  
All Diseases

SummaryWe compared the levels of tissue factor (TF) mRNA in leukocytes with plasma TF antigens of patients in hypercoagulable state caused by various diseases. Flow cytometric analysis showed absence of TF antigen expression on neutrophils and monocytes in healthy subjects but strong expression in both cell types of patients with infections. TF mRNA levels in leukocytes were low in healthy subjects but they were significantly elevated in patients with underlying diseases of disseminated intravascular coagulation (DIC), especially in acute myeloid leukaemia (AML) and infections. TF mRNA levels in leukocytes were significantly high in patients with all diseases except those with thrombosis, and plasma TF antigen levels were significantly high in all diseases. TF mRNA in leukocytes and plasma TF antigen levels were significantly high in patients with overt-DIC, and TF mRNA/antigen ratio was significantly high in patients with overt-DIC. In patients with solid cancers, TF mRNA and TF mRNA/antigen ratio were significantly higher in patients with metastases than those without. TF mRNA levels in leukocytes and plasma levels of TF antigen did not correlate in normal subjects and all patients, but they tended to be correlated in patients with AML, infections or overt-DIC. Our analysis suggests that TF expression in leukocytes plays an important role in various diseases but the expression level does not always correlate with plasma levels of TF antigen.

scholarly journals 3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr−/− mice

2019 ◽  
Vol 116 (12) ◽  
pp. 1948-1957 ◽  
Author(s):  
Martin Berg ◽  
Konstantinos A Polyzos ◽  
Hanna Agardh ◽  
Roland Baumgartner ◽  
Maria J Forteza ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Plasma Lipids ◽  
Nuclear Translocation ◽  
Vascular Inflammation ◽  
Kynurenine Pathway ◽  
Chronic Inflammatory Disease ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Hydroxyanthranilic Acid

Abstract Aims Atherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two major signalling pathways, activation of SREBPs and inflammasome, are associated with the 3-HAA-dependent regulation of lipoprotein synthesis and inflammation in the atherogenesis process. Moreover, we examined whether inhibition of endogenous 3-HAA degradation affects hyperlipidaemia and plaque formation. Methods and results In vitro, we showed that 3-HAA reduces SREBP-2 expression and nuclear translocation and apolipoprotein B secretion in HepG2 cell cultures, and inhibits inflammasome activation and IL-1β production by macrophages. Using Ldlr−/− mice, we showed that inhibition of 3-HAA 3,4-dioxygenase (HAAO), which increases the endogenous levels of 3-HAA, decreases plasma lipids and atherosclerosis. Notably, HAAO inhibition led to decreased hepatic SREBP-2 mRNA levels and lipid accumulation, and improved liver pathology scores. Conclusions We show that the activity of SREBP-2 and the inflammasome can be regulated by 3-HAA metabolism. Moreover, our study highlights that targeting HAAO is a promising strategy to prevent and treat hypercholesterolaemia and atherosclerosis.

scholarly journals Enhanced AP-1 and NF-κB activities and stability of interleukin 8 (IL-8) transcripts are implicated in IL-8 mRNA superinduction in lung epithelial H292 cells

1998 ◽  
Vol 330 (1) ◽  
pp. 429-435 ◽  
Author(s):  
Thierry ROGER ◽  
A. Theo OUT ◽  
Naofumi MUKAIDA ◽  
Kouji MATSUSHIMA ◽  
M. Henk JANSEN ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Dna Binding ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Interleukin 8 ◽  
Mrna Levels ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Inhibitor Of Protein Synthesis

Inhibition of protein synthesis may result in superinduction of short-lived transcripts and has been attributed variably to stabilization of transcripts and/or increased gene transcription. Little is known about the kinetics of these processes and relevant transcriptional elements have not been identified. In this study, we describe superinduction of interleukin 8 (IL-8) mRNA, an important inflammatory mediator, in lung epithelial-like H292 cells and identify the underlying molecular mechanisms and their kinetics. Cycloheximide (CHI, 10 μg/ml), an inhibitor of protein synthesis, maximally increased IL-8 mRNA levels 30-fold in H292 cells. Tumour necrosis factor α (TNF-α), which induced IL-8 mRNA 3-fold, synergized with CHI causing a 150-fold increase at 6 h. CHI early on increased the stability of IL-8 mRNA (from 40 min in cells cultured with medium to more than 4 h with CHI). CHI also increased transcription as shown by transfection with IL-8 promoter constructs. Truncated and mutated constructs identified NF-κB and AP-1 binding sites as primary cis-acting elements in IL-8 gene transcription and IL-8 mRNA superinduction. Electrophoretic mobility shift assays indicated that CHI increased NF-κB and prolonged AP-1 DNA-binding activities and that the synergism of TNF-α and CHI on IL-8 mRNA expression was paralleled by a further increase of AP-1 DNA-binding activity. This synergism was still noticed when 4 h elapsed between the addition of CHI and that of TNF-α. Taken together, our results indicate that CHI interferes with both post-transcriptional and transcriptional repressive mechanisms of IL-8 mRNA expression.

P4484Notch-dependent endothelial dysfunction in patients with aortic valve calcification

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A S Kostina ◽  
D Semenova ◽  
A Kiselev ◽  
O Urtyuga ◽  
T Shcherbinin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Aortic Valve ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Matrix Gla Protein ◽  
Mrna Levels ◽  
Aortic Valve Calcification ◽  
Valve Calcification

Abstract Background Aortic valve calcification associated with either bicuspid or tricuspid aortic valve remains among the most dangerous cardiovascular diseases but cellular and molecular reasons of this pathology are not fully understood. It has been shown that NOTCH1 haploinsufficiency in endothelial cells derived from iPS and also inhibition of NOTCH1 in aortic valve endothelial cells gives rise to the activation of proosteogenic pathways. Endothelial cells regulate underlying interstitial cells and govern them to differentiation. Thus, elucidation of molecular mechanisms of endothelial dysfunction could shed light on valve calcification pathogenesis. Purpose To elucidate key genes responsible for valve endothelial dysfunction in aortic valve calcification. Methods Primary human aortic valve endothelial cells (VEC) were isolated from 45 patients (BAV, n=21; TAV, n=26) with calcific aortic valve disease and from 8 healthy donors. Expression of corresponding genes was estimated by qPCR. Results We checked expression of about 30 genes related to Notch/Wnt/Bmp pathways and shear stress response. Endothelial cells of patients with calcification had significantly lower mRNA levels of Notch component genes NOTCH2, NOTCH3, DLL4 and JAG1 as well as of Notch target genes HEY1, SNAIL and SLUG. Expression of Wnt-related genes such as DKK1, GREM1 and TCF4 was altered in VEC from calcified valves. Interestingly, mRNA level of ROBO4, recently suggested to be involved in endothelial dysfunctions, was significantly higher in VEC of patients with calcification. Moreover, endothelium from calcified valves had impaired expression of matrix gla protein (MGP), which is known to sequester calcium and inhibit soft tissue calcification in the vasculature and aortic valve. Conclusions Our data show that Notch pathway genes are downregulated in valve endothelial cells of the patients with aortic valve calcification. Our results suggest also implication of shear stress responsive genes and genes of endothelial performance in changing the properties of valve endothelial population of calcified valves and thus presumably to the pathogenesis of aortic valve calcification. Acknowledgement/Funding Russian Foundation For Basic Research 18-34-00277

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68

2021 ◽  
pp. jim-2021-001935
Author(s):  
Mohammad Amin Momeni-Moghaddam ◽  
Gholamreza Asadikaram ◽  
Mohammad Masoumi ◽  
Erfan Sadeghi ◽  
Hamed Akbari ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Mrna Levels ◽  
Tnf Α ◽  
Opium Addiction ◽  
Ifn Γ ◽  
Artery Disease

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in patients with CAD with and without opium addiction. This case–control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Sign in / Sign up

Export Citation Format

Share Document