NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease

Wang, Lili; Qü, Ping; Zhao, Jian; Chang, Yeting

doi:10.5114/aoms.2014.44871

Cited by 60 publications

(43 citation statements)

References 30 publications

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“…Similar to our findings in AAA patients, the mRNA levels of NLRP3, CASP1 and IL1B were found to be increased in peripheral blood monocytes from patients with coronary artery disease / atherosclerosis compared with controls (patients with stable angina or acute coronary syndrome, respectively) (15). Thus, the simultaneously increased mRNA levels of NLRP3, CASP1 and IL1B appear to be associated with a systemic proinflammatory state of peripheral blood monocytes in the background of an advanced atherosclerotic disease such as coronary heart disease or AAA.…”

Section: Discussionsupporting

confidence: 77%

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

Cakmak

Wortmann

et al. 2016

Mol Med

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Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sexmatched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients.

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Section: Discussionsupporting

confidence: 77%

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

Cakmak

Wortmann

et al. 2016

Mol Med

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“…Interestingly, miR-22 expression has been found to be decreased in patients with coronary artery disease (CAD) and diseases displaying an inflammatory response [13]. Moreover, NLR family pyrin domain-containing 3 (NLRP3) coupled with downstream cytokines, including caspase-1, increased the severity of CHD and coronary atherosclerosis [14, 15]. Additionally, activation of NLRP3 leading to EC injury is considered a possible mechanism for explaining the deterioration in atherosclerosis [16].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Huang

Wei

Lin

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. Methods: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. Results: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Conclusion: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

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“…NLRP3 gene expression is activated in response to the widest array of exogenous and endogenous stimuli, including microbial agents and other endogenous danger signals, and participate in forming the NLRP3 inflammasome complex, which processes IL-1β and IL-18 secretion to elicit an intense inflammatory response (Guo, et al 2015). In a previous study, NLRP3 mRNA levels correlated significantly with Gensini score, that evaluates the severity of coronary artery disease (Wang, et al 2014). Indeed, NLRP3 mRNA levels correlated with the severity of not only acute illness but also with underlying illness (Wang, et al 2014).…”

Section: Discussionmentioning

confidence: 91%

“…Indeed, NLRP3 mRNA levels correlated with the severity of not only acute illness but also with underlying illness (Wang, et al 2014). NLRP3 mRNA levels level remained elevated during the acute phase of the illness i.e., at 48–72 h, a time point consistent with the assessment of NLRP3 mRNA levels in our study, with subsequent decline (Wang, et al 2014). …”

Section: Discussionmentioning

confidence: 99%

Inflammasome expression and cytomegalovirus viremia in critically ill patients with sepsis

Singh

Inoue

Osawa

et al. 2017

Journal of Clinical Virology

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Background CMV viremia is a contributor to poor outcomes in critically ill patients with sepsis. Objectives To assess the expression levels of genes encoding inflammasome-related proteins in the development of CMV viremia in critically ill patients with sepsis. Study Design A cohort of CMV-seropositive critically ill patients with sepsis due to bloodstream infection underwent weekly testing for CMV viremia. Blood samples to evaluate mRNA levels of genes encoding CASP1, ASC, NLRP1, NLRP3, and NLRP12 were collected at the time of enrollment. Clinical outcomes were assessed at 30 days or until death/discharge from ICU. Results CMV viremia was documented in 27.5% (8/29) of the patients, a median of 7 days after the onset of bacteremia. Patients with sepsis who developed CMV viremia had higher CASP1 although this was not statistically significant (relative mean 3.6 vs 1.8, p=0.13). Development of high grade CMV viremia however, was significantly associated with CASP1; septic patients who developed high grade CMV viremia had significantly higher CASP1 than all other patients (relative mean 5.5 vs 1.8, p=0.016). Conclusions These data document a possible involvement of inflammasomes in the pathogenesis of CMV. Regulating the host immune response by agents that target these genes may have implications for improving CMV-related outcomes in these patients.

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NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease

Cited by 60 publications

References 30 publications

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Inflammasome expression and cytomegalovirus viremia in critically ill patients with sepsis

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