The Correlation between Increased Expressions of NLRP3 Inflammasome Components in Peripheral Blood Mono-Nuclear Cells and Plaque Vulnerability in Human Carotid Atherosclerosis
Abstract
Background: We aimed to determine whether NLRP3 inflammasomes in peripheral blood mononuclear cells (PBMC) were associated with carotid plaque instability in carotid atherosclerosis patients.
Methods: Consecutive 38 carotid atherosclerosis with vulnerable plaques, 22 carotid atherosclerosis with stable plaques, and 40 healthy subjects with no carotid or coronary artery stenosis were enrolled. They were referred to the Second Hospital of Dalian Medical University from 2013-2019. Carotid plaques were evaluated by modified plaque vulnerability risk score (MPVRS) and pathological assessment. The mRNA and protein expression of NLRP3 inflammasome components in PBMC were determined by quantitative real time PCR and Western blot analysis or ELISA.
Results: When consecutive study subjects undergoing carotid endarterectomy were divided into stable (≤4) and unstable (>4) plaque groups according to the MPVRS, the unstable plaque group had significantly raised mRNA and protein expression of NLRP3 inflammasome components in PBMC as compared with the stable plaque group and healthy subject group. Furthermore, subjects with higher NLRP3 protein expression in PBMC had greater incidence of cerebrovascular events.
Conclusions: Increased NLRP3 inflammasome components in PBMC is associated with instability of human carotid atherosclerotic plaques, suggesting NLRP3 inflammasome as a potential biomarker for monitoring carotid plaque instability.
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25. Daskalopoulou SS, Daskalopoulos ME, Per-rea D, Nicolaides AN, Liapis CD (2007). Carotid artery atherosclerosis: What is the evidence for drug action? Curr Pharm Des, 13:1141-1159.
26. Sannino A, Brevetti L, Giugliano G, et al (2014). Non-invasive vulnerable plaque imaging: How do we know that treatment works? Eur Heart J Cardiovasc Imaging, 15:1194-1202.
27. Yla-Herttuala S, Bentzon JF, Daemen M, et al, et al (2011). Stabilisation of atheroscle-rotic plaques. Position paper of the Eu-ropean society of cardiology (esc) work-ing group on atherosclerosis and vascular biology. Thromb Haemost, 106:1-19.
2. Pu Y, Lan L, Leng X, Wong LK, Liu L (2017). Intracranial atherosclerosis: From anatomy to pathophysiology. Int J Stroke, 12(3):236-245.
3. Wang Y, Zhao X, Liu L, et al (2014). Preva-lence and outcomes of symptomatic in-tracranial large artery stenoses and occlu-sions in china: The Chinese intracranial atherosclerosis (cicas) study. Stroke, 45:663-669.
4. Kavurma MM, Rayner KJ, Karunakaran D (2017). The walking dead: Macrophage inflammation and death in atherosclero-sis. Curr Opin Lipidol, 28:91-98.
5. Migdalski A, Jawien A (2021). New in-sight into biology, molecular diagnos-tics and treatment options of unsta-ble carotid atherosclerotic plaque: a narrative review. Ann Transl Med, 9(14):1207.
6. Sager HB, Kessler T, Schunkert H (2017). Monocytes and macrophages in cardiac injury and repair. J Thorac Dis, 9:S30-S35.
7. Silvestre-Roig C, de Winther MP, Weber C, et al (2014). Atherosclerotic plaque desta-bilization: Mechanisms, models, and therapeutic strategies. Circ Res, 114:214-226.
8. Lechareas S, Yanni AE, Golemati S, Chatzi-ioannou A, Perrea D (2016). Ultrasound and biochemical diagnostic tools for the characterization of vulnerable carotid ath-erosclerotic plaque. Ultrasound Med Biol, 42:31-43.
9. Patel AK, Suri HS, Singh J, et al (2016). A re-view on atherosclerotic biology, wall stiffness, physics of elasticity, and its ul-trasound-based measurement. Curr Ather-oscler Rep, 18:83.
10. Yuan J, Usman A, Das T, Patterson AJ, Gillard JH, Graves MJ (2017). Imaging carotid atherosclerosis plaque ulceration: Comparison of advanced imaging mo-dalities and recent developments. AJNR. AJNR Am J Neuroradiol, 38:664-671.
11. Prati P, Tosetto A, Casaroli M, et al (2011). Carotid plaque morphology improves stroke risk prediction: Usefulness of a new ultrasonographic score. Cerebrovasc Dis, 31:300-304.
12. Karlöf E, Buckler A, Liljeqvist ML, et al (2021). Carotid Plaque Phenotyping by Correlating Plaque Morphology from Computed Tomography Angi-ography with Transcriptional Profiling. Eur J Vasc Endovasc Surg, 62(5):716-726.
13. Edsfeldt A, Grufman H, Asciutto G, et al (2015). Circulating cytokines reflect the expression of pro-inflammatory cyto-kines in atherosclerotic plaques. Atheroscle-rosis, 241:443-449.
14. Puz P, Lasek-Bal A (2017). Repeated meas-urements of serum concentrations of tnf-alpha, interleukin-6 and interleukin-10 in the evaluation of internal carotid artery stenosis progression. Atherosclerosis, 263:97-103.
15. Gistera A, Hansson GK (2017). The immu-nology of atherosclerosis. Nat Rev Neph-rol, 13:368-380.
16. Wang L, Qu P, Zhao J, Chang Y (2014). Nlrp3 and downstream cytokine expres-sion elevated in the monocytes of pa-tients with coronary artery disease. Arch Med Sci, 10:791-800.
17. Shi X, Xie WL, Kong WW, Chen D, Qu P (2015). Expression of the nlrp3 inflam-masome in carotid atherosclerosis. J Stroke Cerebrovasc Dis, 24:2455-2466.
18. Stein JH, Korcarz CE, Hurst RT, et al (2008). Use of carotid ultrasound to identify sub-clinical vascular disease and evaluate car-diovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force. Endorsed by the society for vascular medicine. J Am Soc Echocardiogr, 21:93-111.
19. Lee H, Abe Y, Lee I, et al (2014). Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats. Kidney Int, 85:561-569.
20. Hjelmgren O, Gellerman K, Kjelldahl J, Lindahl P, Bergstrom GM (2016). In-creased vascularization in the vulnerable upstream regions of both early and ad-vanced human carotid atherosclerosis. PloS One, 11:e0166918.
21. Ozaki E, Campbell M, Doyle SL (2015). Targeting the nlrp3 inflammasome in chronic inflammatory diseases: Current perspectives. J Inflamm Res, 8:15-27.
22. Li X, Zhang Y, Xia M, Gulbins E, Boini KM, Li PL (2014). Activation of nlrp3 in-flammasomes enhances macrophage li-pid-deposition and migration: Implica-tion of a novel role of inflammasome in atherogenesis. PloS One, 9:e87552.
23. Chen X, Qian S, Hoggatt A, et al (2017). Endothelial cell-specific deletion of p2y2 receptor promotes plaque stability in ath-erosclerosis-susceptible apoe-null mice. Arterioscler Thromb Vasc Biol, 37:75-83.
24. Higashi Y, Sukhanov S, Shai SY, et al (2016). Insulin-like growth factor-1 receptor defi-ciency in macrophages accelerates athero-sclerosis and induces an unstable plaque phenotype in apolipoprotein e-deficient mice. Circulation, 133:2263-2278.
25. Daskalopoulou SS, Daskalopoulos ME, Per-rea D, Nicolaides AN, Liapis CD (2007). Carotid artery atherosclerosis: What is the evidence for drug action? Curr Pharm Des, 13:1141-1159.
26. Sannino A, Brevetti L, Giugliano G, et al (2014). Non-invasive vulnerable plaque imaging: How do we know that treatment works? Eur Heart J Cardiovasc Imaging, 15:1194-1202.
27. Yla-Herttuala S, Bentzon JF, Daemen M, et al, et al (2011). Stabilisation of atheroscle-rotic plaques. Position paper of the Eu-ropean society of cardiology (esc) work-ing group on atherosclerosis and vascular biology. Thromb Haemost, 106:1-19.
| Files | ||
| Issue | Vol 52 No 1 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i1.11677 | |
| Keywords | ||
| Carotid atherosclerosis NLRP3 inflammasome Mononuclear cells Plaque stability | ||
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How to Cite
1.
Xie W, Shi X, Lee H, Wang L, Niu N, Qu P. The Correlation between Increased Expressions of NLRP3 Inflammasome Components in Peripheral Blood Mono-Nuclear Cells and Plaque Vulnerability in Human Carotid Atherosclerosis. Iran J Public Health. 2023;52(1):147-158.
