Enhanced platelet NLRP3 inflammasome expression in patients with acute coronary syndrome and stable coronary artery disease: A prospective observational study : Cardiology Plus

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Enhanced platelet NLRP3 inflammasome expression in patients with acute coronary syndrome and stable coronary artery disease: A prospective observational study

Qi, Zhiyong1; Liu, Xin2; Zhao, Gang1,*; Ge, Junbo1,*

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doi: 10.1097/CP9.0000000000000018
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Abstract

Introduction

Thrombosis in the arterial circulation is the principal pathological cause of arterial thrombotic diseases such as acute coronary syndrome (ACS) and ischemic stroke. Upon injury to blood vessel intima, platelets adhere and aggregate at the site of injury, and may lead to thrombosis and vessel occlusion, resulting in arterial thrombotic diseases[1,2]. Platelets also contribute to the progress of atherosclerosis by interacting with endothelial cells, leukocytes, and endothelial progenitor cells[3,4]. Platelets also contribute to the inflammatory processes in atherosclerosis[5] and promote the formation and progression of atherosclerotic lesion and in vivo thrombosis[6,7].

Nucleotide-binding domain leucine-rich repeat containing protein (NLRP3) is a member of nucleotide-binding oligomerization domain–like receptors (NLRs)[8]. The NLRP3 inflammasome is a critical component of the innate immune system. The NLRP3 inflammasome activates caspase-1 and the secretion of interleukin (IL)-1β and 18 processing[9]. The role of NLRP3 inflammasome in the development and progression of atherosclerosis has been widely documented. Activation of the NLRP3 inflammasome has also been shown in platelets under pathologic conditions that involve inflammation and contributes to thrombus formation[10,11]. In the current study, we compared the expression of platelet NLRP3 inflammasome in patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), versus unstable angina (UA) as well as a group of healthy control subjects.

Materials and Methods

Sixty patients with newly diagnosed ACS (STEMI, NSTEMI, and UA) were recruited between March 2020 and December 2021 from Fudan University Zhongshan Hospital. Sixty patients with stable angina (stable coronary artery disease [CAD] group) and 60 age- and sex-matched subjects undergoing coronary angiography but had normal coronary arteries without stenosis (NCA group) were included as controls. None of the subjects had received antiplatelet, anticoagulant, or anti-inflammatory therapy.

ACS was diagnosed in accordance with the current guidelines[12,13]. The diagnosis of stable angina was based on symptoms plus 50% or more decrease in luminal diameter in one or more coronary arteries.

Patients with malignant tumors, acute or chronic inflammation, or autoimmune diseases were not included in the study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Institutional Review Board, Fudan University Zhongshan Hospital (No. B2020-377; date: February 27, 2020). Written informed consent was obtained from participants before inclusion in the study.

Platelet-rich plasma was prepared as previously described[14] and was filtered through a Sepharose 2B column (Sigma-Aldrich) equilibrated in Tyrode’s solution (pH 7.35) to isolate platelets. NLRP3 inflammasome expression was determined with a NLRP3 PE-conjugated antibody (RD, IC7578P; R&D Systems, Minneapolis, MN) using a FACS (FACSCalibur, Becton Dickinson). IL-1β and IL-18 were determined using an ELISA method (RD, DLB50 and 7620; R&D Systems).

Statistical analysis

Categorical variables are expressed as number and percentage (%), and analyzed using the chi-square test or Fisher exact test, as appropriate. Continuous variables with normal distribution are expressed as mean with standard deviation and analyzed using one-way ANOVA Continuous variables with skewed distribution are expressed as median (interquartile range [IQR]) and analyzed using the Kruskal-Wallis test. Spearman correlation analysis was conducted to examine the association between platelet NLRP3 inflammasome expression with other variables. Multivariate logistic regression was conducted to identify independent risks of ACS. The risk is expressed as odds ratio and 95% confidence intervals (CI).

Statistical analyses were performed using IBM SPSS Statistics, version 19.0 (IBM Co., Armonk, NY) or Prism 7 (GraphPad Inc, San Diego; Differences were considered statistically significant at a 2-sided P < 0.05).

Results

A total of 180 patients were included in the study. Patients were evaluated in NCA, stable CAD, and ACS groups, each containing age- and gender-matched 60 patients, depending on their clinical presentation. Baseline characteristics of the study population, including demographic, clinical, laboratory, and transthoracic echocardiographic parameters, are listed in Table 1. Of the cardiovascular risk factors, prevalence of hypertension (P = 0.008), diabetes mellitus (P < 0.001), and smoking (P = 0.032) were higher in patients with ACS compared to patients with stable CAD and NCA. Compared to others, patients with ACS had higher levels of total cholesterol (P < 0.001), low-density lipoprotein cholesterol (LDL-C) (P < 0.001), white blood cell (WBC) count (P < 0.001), fasting blood glucose (P < 0.001), Hemoglobin A1c (P < 0.001), and NT-proBNP (P < 0.001), as well as a lower level of left ventricular ejection fraction (LVEF) (P < 0.001). However, there were no significant differences among the three groups in terms of triglyceride (P = 0.918), high-density lipoprotein (HDL) (P = 0.089), hemoglobin (P = 0.087), platelet count (P = 0.095), serum creatinine (P = 0.660), left ventricular internal diameter at end-diastole (LVIDd) (P = 0.969), and left ventricular internal diameter at end-systole (LVIDs) (P = 0.225) (Table 1).

Table 1 - Baseline characteristics of study population
Variables NCA (n = 60) Stable CAD (n = 60) ACS (n = 60) P
Age (years) 63.5 ± 10.9 64.7 ± 8.8 63.6 ± 13.9 0.811
Male sex, n (%) 37 (61.7) 38 (63.3) 45 (75.0) 0.241
BMI (kg/m2) 23.03 ± 1.87 23.14 ± 1.15 23.29 ± 1.22 0.481
Hypertension, n (%) 23 (38.3) 31 (51.7) 40 (66.7) 0.008
Diabetes mellitus, n (%) 6 (10.0) 15 (25.0) 26 (43.3) <0.001
Smoking, n (%) 15 (25.0) 18 (30.0) 28 (46.7) 0.032
Total cholesterol (mmol/L) 4.32 ± 1.01 3.58 ± 0.81 4.51 ± 1.09 <0.001
Triglyceride (mmol/L) 1.70 ± 1.20 1.73 ± 1.15 1.63 ± 1.43 0.918
LDL-C (mmol/L) 2.31 ± 0.85 1.70 ± 0.76 2.76 ± 1.10 <0.001
HDL (mmol/L) 1.28 ± 0.50 1.15 ± 0.36 1.10 ± 0.50 0.089
Hemoglobin (g/L) 134.9 ± 14.5 132.4 ± 13.2 137.8 ± 12.0 0.087
WBC count (*109/L) 5.81 ± 1.31 6.21 ± 1.36 9.88 ± 3.57 <0.001
Platelet count (*109/L) 200.8 ± 52.5 212.2 ± 57.4 225.6 ± 74.2 0.095
Serum creatinine (μmol/L) 79.6 ± 21.8 76.7 ± 22.0 79.7 ± 17.8 0.660
Fasting blood glucose (mmol/L) 6.1 ± 2.0 6.9 ± 2.6 8.2 ± 2.5 <0.001
Hemoglobin A1c (%) 5.82 ± 0.68 6.47 ± 1.28 6.78 ± 1.35 <0.001
Troponin-T (ng/mL)
 Baseline 1.40 ± 1.70
 Peak 3.54 ± 3.67
Creatine kinase-myocardial band (U/L)
 Baseline 35.1 ± 26.5
 Peak 157.3 ± 271.0
NT-proBNP (pg/mL) 264.0 ± 409.0 294.0 ± 449.2 1125.0 ± 974.3 <0.001
LVEF (%) 64.7 ± 6.3 60.0 ± 9.9 53.9 ± 8.8 <0.001
LVIDd (mm) 48.5 ± 7.4 48.8 ± 6.0 48.8 ± 6.2 0.969
LVIDs (mm) 31.3 ± 7.2 32.9 ± 6.4 33.4 ± 6.6 0.225
Data are presented as mean ± standard deviation or proportions.
ACS: acute coronary syndrome; BMI: body mass index; CAD: coronary artery disease; HDL: high-density lipoprotein; LDL-C: low-density lipoprotein cholesterol; LVEF: left ventricular ejection fraction; LVIDd: left ventricular internal diameter at end-diastole; LVIDs: left ventricular internal diameter at end-systole; NCA: normal coronary arteries; NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3; WBC: white blood cell.

Platelet NLRP3 expression was greater in patients with ACS compared to those with stable CAD and NCA, and patients with stable CAD also had higher levels of platelet NLRP3 as compared to those with NCA (Figure 1). In addition, compared to patients with stable CAD and NCA, both plasma IL-1β and IL-18 levels were raised in patients with ACS. And patients with stable CAD also had higher plasma levels of IL-1β and IL-18 as compared to those with NCA (Table 2). Both of the plasma levels of IL-1β and IL-18 were positively correlated with platelet NLRP3 expression (r = 0.662, P < 0.001; r = 0.324, P < 0.001, respectively; Figure 2). However, platelet NLRP3 expressions in patients with STEMI (n=26), NSTEMI (n=21), and UA (n=13) did not differ among groups (48.0 ± 21.4 vs. 42.4 ± 20.9 vs. 41.6 ± 22.4, P = 0.563).

Table 2 - Platelet NLRP3 expression and plasma levels of IL-1β and IL-18 in patients with NCA, stable CAD, and ACS
Variables NCA (n = 60) Stable CAD (n = 60) ACS (n = 60) P
NLRP3 (%) 12.4 ± 7.2 25.9 ± 15.9 44.7 ± 21.3 <0.001
IL-1β (pg/mL) 0.76 ± 0.67 1.43 ± 1.09 3.72 ± 2.83 <0.001
IL-18 (pg/mL) 63.49 ± 33.71 131.19 ± 53.93 201.55 ± 96.32 <0.001
Data are presented as mean ± standard deviation.
ACS: acute coronary syndrome; CAD: coronary artery disease; IL: interleukin; NCA: normal coronary arteries; NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3.

F1
Figure 1.:
Platelet NLRP3 expression in patients with NCA, stable CAD, and ACS. ACS: acute coronary syndrome; CAD: coronary artery disease; NCA: normal coronary arteries; NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3; SA: stable angina.
F2
Figure 2.:
Correlation of platelet NLRP3 expression and plasma levels of IL-1β and IL-18 in patients. A, Correlation of platelet NLRP3 expression and plasma levels of IL-1β in patients with NCA, stable CAD, and ACS. B, Correlation of platelet NLRP3 expression and plasma levels of and IL-18 in patients with NCA, stable CAD, and ACS. IL: interleukin; NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3; ACS: acute coronary syndrome; CAD: coronary artery disease; NCA: normal coronary arteries.

Levels of platelet NLRP3 expression were found to be higher in patients with hypertension (P = 0.042), diabetes mellitus (P < 0.001), and smoking (P = 0.015), while the levels of which showed no difference between men and women (P = 0.331) (Table 3). Correlation analyses between platelet NLRP3 expression and baseline characteristics were provided in Table 4. WBC count, fasting blood glucose, hemoglobin A1c, and NT-proBNP were positively and LVEF was inversely correlated with platelet NLRP3 expression.

Table 3 - Comparison of platelet NLRP3 expression regarding the presence of conventional cardiovascular risk factors
Variables No. NLRP3 (%) P
Sex
 Male 120 28.7 ± 20.5 0.331
 Female 60 25.6 ± 21.0
Hypertension
 − 86 24.4 ± 18.5 0.042
 + 94 30.7 ± 22.1
Diabetes mellitus
 − 133 23.8 ± 19.0 <0.001
 + 47 38.8 ± 21.2
Smoking
 − 119 25.0 ± 19.5 0.015
 + 61 32.9 ± 22.0
Data are presented as mean ± standard deviation.
NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3.

Table 4 - Correlation between baseline characteristics and platelet NLRP3 expression
Variables Spearman’s rho P
LDL-C (mmol/L) 0.077 0.313
HDL (mmol/L) −0.128 0.093
White blood cell count (*109/L) 0.361 <0.001
Platelet count (*109/L) 0.045 0.544
Fasting blood glucose (mmol/L) 0.172 0.021
Hemoglobin A1c (%) 0.173 0.031
Baseline troponin-T (ng/mL) 0.013 0.395
Peak troponin-T (ng/mL) 0.001 0.836
Baseline creatine kinase- myocardial band (U/L) 0.036 0.157
Peak creatine kinase-myocardial band (U/L) 0.001 0.837
NT-proBNP (pg/mL) 0.360 <0.001
LVEF (%) −0.273 <0.001
HDL: high-density lipoprotein; LDL-C: low-density lipoprotein cholesterol; LVEF: left ventricular ejection fraction. NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3.

In the univariate analysis, we found that platelet NLRP3 expression was independently associated with ACS occurrence in relative to NCA and stable CAD (Table 5). In the multivariate analysis, platelet NLRP3 expression was also found to be independently associated with ACS occurrence in relative to NCA (OR = 1.23, P = 0.006) and stable CAD (OR = 1.06, P = 0.002), while adjusted for hypertension, diabetes mellitus, smoking, LDL-C, HDL, fasting blood glucose, hemoglobin A1c, and so on.

Table 5 - Univariate logistic regression analysis for risk factors of ACS
Variables ACS vs. NCA ACS vs. stable CAD
OR 95% CI P OR 95% CI P
Age (years) 1.00 0.97–1.03 0.988 0.99 0.96–1.02 0.586
Male 1.87 0.85–4.08 0.119 1.74 0.79–3.81 0.168
BMI (kg/m2) 0.96 0.76–1.21 0.701 0.90 0.71–1.14 0.367
Hypertension 3.22 1.52–6.80 0.002 1.87 0.90–3.91 0.096
Diabetes mellitus 6.88 2.57–18.45 <0.001 2.29 1.06–4.99 0.036
Smoking 2.63 1.21–5.69 0.015 2.04 0.97–4.32 0.062
LDL-C (mmol/L) 1.64 1.07–2.51 0.022 3.94 2.24–6.93 <0.001
HDL (mmol/L) 0.43 0.18–1.06 0.066 0.76 0.32–1.84 0.549
Fasting blood glucose (mmol/L) 1.57 1.26–1.94 <0.001 1.25 1.06–1.46 0.007
Hemoglobin A1c (%) 3.05 1.70–2.51 0.022 1.20 0.89–1.62 0.236
NLRP3 (%) 1.16 1.10–1.23 <0.001 1.05 1.03–1.08 <0.001
ACS: acute coronary syndrome; BMI: body mass index; CAD: coronary artery disease; CI: confidence interval; HDL: high-density lipoprotein; LDL-C: low-density lipoprotein cholesterol; NCA: normal coronary arteries; NLRP3: nucleotide-binding domain leucine-rich repeat containing protein 3; OR: odds ratio.

Discussion

Major findings of the current study include: (1) platelet NLRP3 inflammasome expression was enhanced in patients with ACS compared to patients with stable CAD and NCA; (2) higher NLRP3 inflammasome expression correlated with higher plasma levels of IL-1β and IL-18; (3) platelet NLRP3 inflammasome expression was higher in patients with conventional cardiovascular risk factors (e.g., hypertension, diabetes mellitus, and smoking); (4) platelet NLRP3 inflammasome expression was an independent predictor of ACS risk.

Inflammation is an important driver of atherosclerosis development and progression (plaque destabilization and rupture), and involves complex interaction among various biochemical, intracellular, and extracellular processes[15]. IL-1β and IL-18 are members of the IL-1 family and critical components of both the innate and adaptive immune responses[16]. IL-1β and IL-18 play vital roles in inflammation in atherosclerotic progression[17,18]. The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) trial demonstrated blocking IL-1β with monoclonal IL-1β–neutralizing antibody canakinumab is a viable approach for treating atherosclerotic diseases[19]. NLRP3 inflammasome activates cathepsin-B and downstream cytokines IL-1β and IL-18[20]. Zheng et al found NLRP3 overexpression in the aorta of patients with coronary atherosclerosis and a correlation between aortic NLRP3 expression with the severity of coronary artery disease and other atherosclerotic risk factors[21]. Shi et al showed that the expression of NLRP3, IL-1β, and IL-18 is associated with plaque vulnerability and atherogenesis[22]. Varghese et al found significantly higher NLRP3 expression in symptomatic versus asymptomatic CVD patients[23]. Afrasyab et al found a correlation between higher peripheral blood monocyte NLRP3 and more severe coronary atherosclerosis.[24] They also showed NLRP3 level in peripheral blood monocytes could be used to predict major adverse cardiac events[24]. Wang et al found that the expression of monocyte NLRP3 and downstream cytokines are associated with increasing severity of coronary artery disease, as reflected by higher Gensini score[25]. Altaf et al found higher NLRP3 in peripheral blood monocytes and downstream cytokines (IL-1β and IL-18) in patients with ACS versus stable CVD[26]. The current study extended such an association to platelet NLRP3 expression and ACS.

Platelets are critical mediators of atherosclerosis and thrombosis and can act both locally and systemically to promote inflammation[6,27]. Upon infection with bacteria and virus, activated platelet NLRP3 triggers the release of IL-1β and increase vascular permeability[28]. Additionally, NLRP3 contributes to platelet activation, aggregation and thrombus formation in vitro[10]. Moreover, NLRP3 regulates platelet integrin αIIbβ3 outside-in signaling, hemostasis and arterial thrombosis by a mechanism that involves IL-1β[11]. Consistent with the prothrombotic state in ACS, the current study demonstrated higher expression of platelet NLRP3 in patients with ACS versus stable CAD and NCA. We also found higher platelet NLRP3 expression in patients with stable CAD versus NCA, suggesting a role of platelet NLRP3 in atherosclerosis in addition to thrombosis. A previous study by Gurses et al found enhanced expression of pattern recognition receptors (e.g., toll-like receptor s2 and 4) in platelets in patients with ACS versus stable CAD and NCA[29]. Taken together, these results suggest platelet NLRP3 as a pivotal molecular link between inflammation, atherosclerosis, and thrombosis.

There are ongoing efforts in developing NLRP3 inhibitors as treatment for CVD[30]. Selective NLRP3 inhibition using MCC950 has been shown to be a promising therapeutic approach to inhibit atherosclerotic lesion development[31]. The NLRP3 inhibitor CY-09 has also been shown to inhibit platelet activation and arterial thrombosis[11].

Blocking NLRP3 inflammatory bodies has been shown to improve cardiac remodeling and reduce left ventricular systolic dysfunction in a mouse model[32]. Decreased LVEF and elevated NT-proBNP are risk factors that predict poor long-term prognosis in ACS patients[33]. The current study confirmed association between platelet NLRP3 expression and LVEF and NT-proBNP, supporting the use of platelet NLRP3 expression in the prediction of prognosis.

The present study had several limitations. First, sample size is relatively small. Second, patient selection bias is inherent to such observational study. Further studies with larger sample size and prospective design are needed to verify our findings.

CONCLUSION

Platelet NLRP3 expression is highest in patients with ACS, followed by stable CAD, and lowest in NCA. These findings suggest an important role of platelet NLRP3 in the process of atherosclerosis as well as thrombosis.

FUNDING

This study was supported by the National Natural Science Foundation of China (No. 82100355), the Shanghai Sailing Program (no. 21YF1406000), the Chinese Cardiovascular Association-Access fund (no. 2020-CCA-ACCESS-030), and the China Postdoctoral Science Foundation (No. 2021M700827).

AUTHOR CONTRIBUTIONS

ZQ, XL, GZ and JG participated in the research design and the performance of the research. ZQ and XL contributed new reagents or analytic tools and participated in data analysis. ZQ and XL participated in the writing of the paper, and JG and GZ revised the paper.

CONFLICTS OF INTEREST STATEMENT

Junbo Ge is the Editor-in-Chief of Cardiology Plus. The article was subject to the journal’s standard procedures, with peer review handled independently of this Editorial Board member and their research groups.

REFERENCES

[1]. Ruggeri ZM. Platelets in atherothrombosis. Nat Med. 2002;8:1227–1234. doi:10.1038/nm1102-1227.
[2]. Gurbel PA, Jeong YH, Navarese EP, et al. Platelet-mediated thrombosis: from bench to bedside. Circ Res. 2016;118:1380–1391. doi:10.1161/CIRCRESAHA.115.307016.
[3]. Lindemann S, Krämer B, Seizer P, et al. Platelets, inflammation and atherosclerosis. J Thromb Haemost. 2007;5:203–211. doi:10.1111/j.1538-7836.2007.02517.x.
[4]. Barrett TJ, Schlegel M, Zhou F, et al. Platelet regulation of myeloid suppressor of cytokine signaling 3 accelerates atherosclerosis. Sci Transl Med. 2019;11:eaax0481. doi:10.1126/scitranslmed.aax0481.
[5]. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126. doi:10.1056/NEJM199901143400207.
[6]. Wagner DD, Burger PC. Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol. 2003;23:2131–2137. doi:10.1161/01.ATV.0000095974.95122.EC.
[7]. von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res. 2007;100:27–40. doi:10.1161/01.RES.0000252802.25497.b7.
[8]. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. doi:10.1016/j.cell.2006.02.015.
[9]. Cassel SL, Joly S, Sutterwala FS. The NLRP3 inflammasome: a sensor of immune danger signals. Semin Immunol. 2009;21:194–198. doi:10.1016/j.smim.2009.05.002.
[10]. Murthy P, Durco F, Miller-Ocuin JL, et al. The NLRP3 inflammasome and bruton’s tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation. Biochem Biophys Res Commun. 2017;483:230–236. doi:10.1016/j.bbrc.2016.12.161.
[11]. Qiao J, Wu X, Luo Q, et al. NLRP3 regulates platelet integrin αIIbβ3 outside-in signaling, hemostasis and arterial thrombosis. Haematologica. 2018;103:1568–1576. doi:10.3324/haematol.2018.191700.
[12]. Ibanez B, James S, Agewall S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39:119–177. doi:10.1093/eurheartj/ehx393.
[13]. Rapezzi C, Biagini E, Branzi A. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: the task force for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes of the European Society of Cardiology. Eur Heart J. 2008;29:277–278. doi:10.1093/eurheartj/ehm498.
[14]. Zhang S, Ye J, Zhang Y, et al. P2Y12 protects platelets from apoptosis via PI3k-dependent Bak/Bax inactivation. J Thromb Haemost. 2013;11:149–160. doi:10.1111/jth.12063.
[15]. Bäck M, Yurdagul A Jr, Tabas I, et al. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat Rev Cardiol. 2019;16:389–406. doi:10.1038/s41569-019-0169-2.
[16]. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281:8–27. doi:10.1111/imr.12621.
[17]. Galea J, Armstrong J, Gadsdon P, et al. Interleukin-1 beta in coronary arteries of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol. 1996;16:1000–1006. doi:10.1161/01.atv.16.8.1000.
[18]. Mallat Z, Corbaz A, Scoazec A, et al. Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability. Circ Res. 2001;89:E41–E45. doi:10.1161/hh1901.098735.
[19]. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–1131. doi:10.1056/NEJMoa1707914.
[20]. Grebe A, Hoss F, Latz E. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ Res. 2018;122:1722–1740. doi:10.1161/CIRCRESAHA.118.311362.
[21]. Zheng F, Xing S, Gong Z, et al. NLRP3 inflammasomes show high expression in aorta of patients with atherosclerosis. Heart Lung Circ. 2013;22:746–750. doi:10.1016/j.hlc.2013.01.012.
[22]. Shi X, Xie WL, Kong WW, et al. Expression of the NLRP3 inflammasome in carotid atherosclerosis. J Stroke Cerebrovasc Dis. 2015;24:2455–2466. doi:10.1016/j.jstrokecerebrovasdis.2015.03.024.
[23]. Paramel VG, Folkersen L, Strawbridge RJ, et al. NLRP3 inflammasome expression and activation in human atherosclerosis. J Am Heart Assoc. 2016;5:e003031. doi:10.1161/JAHA.115.003031.
[24]. Afrasyab A, Qu P, Zhao Y, et al. Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in acute coronary syndrome patients. Heart Vessels. 2016;31:1218–1229. doi:10.1007/s00380-015-0723-8.
[25]. Wang L, Qu P, Zhao J, et al. NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease. Arch Med Sci. 2014;10:791–800. doi:10.5114/aoms.2014.44871.
[26]. Altaf A, Qu P, Zhao Y, et al. NLRP3 inflammasome in peripheral blood monocytes of acute coronary syndrome patients and its relationship with statins. Coron Artery Dis. 2015;26:409–421. doi:10.1097/MCA.0000000000000255.
[27]. Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357:2482–2494. doi:10.1056/NEJMra071014.
[28]. Hottz ED, Lopes JF, Freitas C, et al. Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation. Blood. 2013;122:3405–3414. doi:10.1182/blood-2013-05-504449.
[29]. Gurses KM, Kocyigit D, Yalcin MU, et al. Enhanced platelet toll-like receptor 2 and 4 expression in acute coronary syndrome and stable angina pectoris. Am J Cardiol. 2015;116:1666–1671. doi:10.1016/j.amjcard.2015.08.048.
[30]. Baldwin AG, Brough D, Freeman S. Inhibiting the inflammasome: a chemical perspective. J Med Chem. 2016;59:1691–1710. doi:10.1021/acs.jmedchem.5b01091.
[31]. van der Heijden T, Kritikou E, Venema W, et al. NLRP3 inflammasome inhibition by MCC950 reduces atherosclerotic lesion development in apolipoprotein E-deficient mice-brief report. Arterioscler Thromb Vasc Biol. 2017;37:1457–1461. doi:10.1161/ATVBAHA.117.309575.
[32]. Carbone S, Mauro AG, Prestamburgo A, et al. An orally available NLRP3 inflammasome inhibitor prevents western diet-induced cardiac dysfunction in mice. J Cardiovasc Pharmacol. 2018;72:303–307. doi:10.1097/FJC.0000000000000628.
[33]. Hamada S, Schroeder J, Hoffmann R, et al. Prediction of outcomes in patients with chronic ischemic cardiomyopathy by layer-specific strain echocardiography: a proof of concept. J Am Soc Echocardiogr. 2016;29:412–420. doi:10.1016/j.echo.2016.02.001.
Keywords:

Blood platelets; NLRP3; Acute coronary syndrome; Coronary artery disease

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