Cigarette smoking induces activation of NLRP3 inflammasome assembly in peripheral blood monocytes of patients with coronary artery disease.

SummaryThe arachidonic acid metabolites participate in development of coronary artery disease (CAD) and the plaque’s instability.We assessed two common genetic polymorphisms: of cyclooxyge-nase-2 (COX-2) (COX 2.8473, rs5275) and prostaglandin EP2 receptor gene (uS5, rs708494) in patients with CAD. Out of 1,368 patients screened by coronary arteriography, two groups fulfilled the entry criteria and were studied: stable coronary disease (sCAD, n=125) and acute coronary syndromes (ACS, n=63).They did not differ in the main characteristics.All patients were on aspirin at least seven days prior to the study.In 70 control subjects, the same genotypes were ascertained, expression of cyclooxygenases in peripheral blood monocytes was assessed by flow cytometry, and in-vitro biosynthesis of PGE2 was measured by mass spectrometry. COX-2 CC homozygotes (variant allele), were more common, while EP2 GG homozygotes (wild-type) were less common in ACS (p=0.03 and p=0.017) than in the sCAD group.A combined genotype characterized by the presence of the wild-type COX2.8743T allele and the wild type homozygous EP2uS5 genotype (TT or CT | GG) decreased risk ratio of ACS in CAD patients (relative risk 0.41;95% confidence interval 0.21–0.81).COX-2 polymorphism in control subjects did not affect the enzyme expression or PGE2 production by peripheral blood monocytes, but production of PGE2 increased by 40.1% in the subjects homozygous for EP2 receptor allele uS5A following lipopolysaccharide stimulation. In conclusion, the combined COX-2 (COX 2.8473) and the EP2 receptor (uS5) genotypes seem to influence CAD stability, but in peripheral blood monocytes only EP2 receptor modulates PGE2 production.

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W13-P-018 Toll-like receptor 4 expression on peripheral blood monocytes predicts the risk of coronary artery disease in patients with low C-reactive protein

Atherosclerosis Supplements ◽

10.1016/s1567-5688(05)80355-1 ◽

2005 ◽

Vol 6 (1) ◽

pp. 89-90

Author(s):

R. Shiraki ◽

N. Inoue ◽

K. Otsui ◽

T. Honjo ◽

M. Takahashi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Peripheral Blood ◽

Toll Like Receptor ◽

Blood Monocytes ◽

C Reactive Protein ◽

Toll Like Receptor 4 ◽

Peripheral Blood Monocytes ◽

Reactive Protein ◽

Artery Disease

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

Clinical Science ◽

10.1042/cs20130043 ◽

2013 ◽

Vol 126 (3) ◽

pp. 233-241 ◽

Cited By ~ 57

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.

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High retinoic acid receptor-related orphan receptor A gene expression in peripheral blood leukocytes may be related to acute myocardial infarction

Journal of International Medical Research ◽

10.1177/03000605211019663 ◽

2021 ◽

Vol 49 (6) ◽

pp. 030006052110196

Author(s):

Heyu Meng ◽

Jianjun Ruan ◽

Xiaomin Tian ◽

Lihong Li ◽

Weiwei Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Acute Myocardial Infarction ◽

Coronary Artery ◽

Peripheral Blood ◽

Retinoic Acid Receptor ◽

Stable Coronary Artery Disease ◽

Orphan Receptor ◽

Blood Leukocytes ◽

Artery Disease

Objective This study aimed to investigate whether differential expression of the retinoic acid receptor-related orphan receptor A ( RORA) gene is related to occurrence of acute myocardial infarction (AMI). Methods This was a retrospective study. White blood cells of 93 patients with acute myocardial infarction and 74 patients with stable coronary artery disease were collected. Reverse transcription quantitative polymerase chain reaction and western blotting were used to measure RORA mRNA and protein expression, respectively. Results RORA mRNA expression levels in peripheral blood leukocytes in patients with AMI were 1.57 times higher than those in patients with stable coronary artery disease. Protein RORA levels in peripheral blood of patients with AMI were increased. Binary logistic regression analysis showed that high expression of RORA was an independent risk factor for AMI, and it increased the risk of AMI by 2.990 times. Conclusion RORA expression levels in patients with AMI is significantly higher than that in patients with stable coronary artery disease. High expression of RORA is related to AMI and it may be an independent risk factor for AMI.

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