Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease
- PMID: 32585928
- PMCID: PMC7352274
- DOI: 10.3390/ijms21124459
Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease
Abstract
Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1β pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this complex pathway is activated by a number of factors, such as unhealthy nutrition, altered gut and oral microbiota, and elevated cholesterol itself. Moreover, evidence from autoinflammatory diseases, like psoriasis and others, which are also associated with higher cardiovascular disease (CVD) risk, suggests that variants of NLRP3 pathway-related genes (like NLRP3 itself, caspase recruitment domain-containing protein (CARD)8, caspase-1 and IL-1β) may carry gain-of-function mutations leading, in some individuals, to a constitutive pro-inflammatory pattern. Indeed, some reports have recently associated the presence of specific single nucleotide polymorphisms (SNPs) on such genes with greater ASCVD prevalence. Based on these observations, a potential effective strategy in this context may be the identification of carriers of these NLRP3-related SNPs, to generate a genomic score, potentially useful for a better CVD risk prediction, and, possibly, for personalized therapeutic approaches targeted to the NLRP3-IL-1β pathway.
Keywords: NLRP3 inflammasome; atherosclerosis; cardiovascular disease; interleukin-1β; low-grade inflammation; single nucleotide polymorphism.
Conflict of interest statement
A.B.: no conflict of interest. A.L.C. has received honoraria, lecture fees, or research grants from: Akcea, Amgen, Astrazeneca, Eli Lilly, Genzyme, Kowa, Mediolanum, Menarini, Merck, Pfizer, Recordati, Sanofi, Sigma Tau, Medco, Amryt. P.M.: has received honoraria, lecture fees, or research grants from: Montefarmaco OTC, Bayer.
Figures
Similar articles
-
Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis, and Atherogenesis.Circulation. 2018 Aug 28;138(9):898-912. doi: 10.1161/CIRCULATIONAHA.117.032636. Circulation. 2018. PMID: 29588315 Free PMC article.
-
Genetic and Epigenetic Regulation of the Innate Immune Response to Gout.Immunol Invest. 2023 Apr;52(3):364-397. doi: 10.1080/08820139.2023.2168554. Epub 2023 Feb 6. Immunol Invest. 2023. PMID: 36745138 Review.
-
Interleukin-1β suppression dampens inflammatory leucocyte production and uptake in atherosclerosis.Cardiovasc Res. 2022 Oct 21;118(13):2778-2791. doi: 10.1093/cvr/cvab337. Cardiovasc Res. 2022. PMID: 34718444 Free PMC article.
-
NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis.Circ Res. 2018 Jun 8;122(12):1722-1740. doi: 10.1161/CIRCRESAHA.118.311362. Circ Res. 2018. PMID: 29880500 Review.
-
Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease.Circ Res. 2020 Apr 24;126(9):1260-1280. doi: 10.1161/CIRCRESAHA.120.315937. Epub 2020 Apr 23. Circ Res. 2020. PMID: 32324502 Free PMC article. Review.
Cited by
-
Chemical Modulation of the 1-(Piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Scaffold as a Novel NLRP3 Inhibitor.Molecules. 2021 Jun 29;26(13):3975. doi: 10.3390/molecules26133975. Molecules. 2021. PMID: 34209843 Free PMC article.
-
The role of the gut microbiota in health and cardiovascular diseases.Mol Biomed. 2022 Oct 11;3(1):30. doi: 10.1186/s43556-022-00091-2. Mol Biomed. 2022. PMID: 36219347 Free PMC article. Review.
-
Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis.Int J Mol Sci. 2020 Oct 30;21(21):8145. doi: 10.3390/ijms21218145. Int J Mol Sci. 2020. PMID: 33143375 Free PMC article. Review.
-
Oral Porphyromonas gingivalis and Fusobacterium nucleatum Abundance in Subjects in Primary and Secondary Cardiovascular Prevention, with or without Heterozygous Familial Hypercholesterolemia.Biomedicines. 2022 Aug 31;10(9):2144. doi: 10.3390/biomedicines10092144. Biomedicines. 2022. PMID: 36140246 Free PMC article.
-
Portrayal of NLRP3 Inflammasome in Atherosclerosis: Current Knowledge and Therapeutic Targets.Int J Mol Sci. 2023 May 3;24(9):8162. doi: 10.3390/ijms24098162. Int J Mol Sci. 2023. PMID: 37175869 Free PMC article. Review.
References
-
- Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckert E., Hegele R.A., Krauss R.M., Raal F.J., Schunkert H., et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2017;38:2459–2472. doi: 10.1093/eurheartj/ehx144. - DOI - PMC - PubMed
-
- Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., Chapman M.J., De Backer G.G., Delgado V., Ference B.A., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur. Heart J. 2019;290:140–205. doi: 10.1016/j.atherosclerosis.2019.08.014. - DOI - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical