NLRP3 inflammasome activation in coronary artery disease: results from prospective and randomized study of treatment with atorvastatin or rosuvastatin

2013 ◽  
Vol 126 (3) ◽  
pp. 233-241 ◽  
Author(s):  
Mamoru Satoh ◽  
Tsuyoshi Tabuchi ◽  
Tomonori Itoh ◽  
Motoyuki Nakamura
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Nlrp3 Inflammasome ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Randomized Study ◽  
Inflammasome Activation ◽  
Randomized Clinical Study ◽  
Artery Disease

The NLRP-3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome has recently emerged as a pivotal regulator of chronic inflammation. The aim of the present study was to determine whether NLRP3 inflammasome is expressed in patients with CAD (coronary artery disease) and whether statins (atorvastatin or rosuvastatin) might affect NLRP3 levels. In an in vitro study, human THP-1 cells treated with statins were analysed for NLRP3 inflammasome levels. The present study included 60 patients with CAD and 30 subjects without CAD (non-CAD). Patients with CAD randomly received either 8 months of treatment with atorvastatin or rosuvastatin. PBMCs (peripheral blood mononuclear cells) were obtained from peripheral blood at baseline and after 8 months of statin therapy. Levels of NLRP3 inflammasome, IL (interleukin)-1β and IL-18 were measured by real-time RT–PCR (reverse transcription–PCR) and FACS. Levels of NLRP3 inflammasome were higher in the CAD group than in the non-CAD group. There was a positive correlation between NLRP3 inflammasome and cytokines (IL-1β and IL-18) levels. A randomized clinical study has shown that atorvastatin markedly diminished NLRP3 inflammasome levels, whereas rosuvastatin had no impact on these levels. Levels of NLRP3 inflammasome decreased in THP-1 cells treated with statins compared with those treated with vehicle, and the fold changes in NLRP3 inflammasome were higher in THP-1 cells treated with atorvastatin compared with those treated with rosuvastatin. The present study suggests that atorvastatin down-regulates NLRP3 inflammasome expression in CAD, possibly contributing to the inhibitory effects of atorvastatin on chronic inflammation and atherogenic progression in this disorder.

scholarly journals Up-regulated lncRNA-PVT1 Expression in Peripheral Blood Mononuclear Cells of Patients with Coronary Artery Disease is Correlated with Decreased Interleukin-10 Production

2020 ◽  
Author(s):  
Behnoosh Miladpour ◽  
Atefeh Seghatoleslam ◽  
mehdi kalani ◽  
Mehran Erfani ◽  
peyman Nowrouzi-Sohrabi
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Blood Mononuclear Cells ◽  
Artery Disease

Abstract Background: Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA (lncRNA), and it has not been previously studied in the inflammatory responses of peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD). Methods: This cross-sectional study was conducted in 15 CAD patients and 15 non-CAD (NCAD) individuals. PVT1 expression in PBMCs of the participants was measured, using real-time PCR. Interleukin (IL)-10, IL-22 and MMP-9 in the plasma and supernatant of the cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) was assessed, using flowcytometry and ELISA.Results: An increased expression of PVT1 was observed in untreated PBMCs of CAD patients compared to the NCAD group. There was a significant up-regulation of PVT1 after LPS treatment in PBMCs of both groups. Plasma matrix metalloproteinase-9 (MMP-9) levels were found to be higher in CAD patients compared to the controls. The level of IL-10 and IL-22 production from the non-treated PBMCs of CAD was significantly lower compared to the NCAD group. In the total examined population, PVT1 expression was negatively correlated with IL-10 secretion. The results also showed a significant negative correlation between PVT1 expression and IL-10 produced by untreated cells. Conclusions: PVT1 expression is increased in PBMCs of CAD patients and this increased expression could be associated with decreased IL-10 production from PBMCs of these patients.

Characteristics of circular RNAs expression of peripheral blood mononuclear cells in humans with Coronary Artery Disease

2021 ◽  
Author(s):  
Wen-Feng Ji ◽  
Jia-Xin Chen ◽  
Shu He ◽  
Ya-Qing Zhou ◽  
Lei Hua ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Artery Disease

Objective: Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). Methods: We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of 5 CAD patients and 5 controls. Bioinformatics analyses was adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the miRNA targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. Results: In total, 13160 downregulated and 12905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle and cellular metabolic process. Parental genes of the 10 dysregulated-circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into diagnosis and prognosis of coronary artery disease.

Association of peripheral blood mononuclear cells adenylate cyclase-associated protein 1 mRNA with coronary artery disease

2016 ◽  
Vol 252 ◽  
pp. e246-e247
Author(s):  
M. Sopic ◽  
J. Joksić ◽  
V. Spasojević Kalimanovska ◽  
D. Kalminaovska Oštrić ◽  
K. Anđelković ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Adenylate Cyclase ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Artery Disease

Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality

2021 ◽  
Author(s):  
Stefan J Schunk ◽  
Marcus E Kleber ◽  
Winfried März ◽  
Shichao Pang ◽  
Stephen Zewinger ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systemic Inflammation ◽  
Cardiovascular Mortality ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Amyloid A ◽  
Nlrp3 Inflammasome Activation ◽  
Artery Disease ◽  
Genetically Determined

Abstract Aims Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown. Methods and results We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality. Conclusion The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.

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