Cited by 382Inflammasome and immune disordersAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways

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Koushki, Khadijeh, Shahbaz, Sanaz Keshavarz, Mashayekhi, Kazem, Sadeghi, Mahvash, Zayeri, Zeinab Deris, Taba, Mahdieh Yousefi, Banach, Maciej, Al-Rasadi, Khalid +2 more·2021·Clinical Reviews in Allergy & Immunology

Abstract

Atherosclerosis is one type of cardiovascular disease (CVD) in which activation of the NLRP3 inflammasome and toll-like receptor (TLR) pathways is implicated. One of the most effective treatments for atherosclerosis is the use of statin medications. Recent studies have indicated that statins, in addition to their lipid-lowering effects, exert inhibitory and/or stimulatory effects on the NLRP3 inflammasome and TLRs. Some of the statins lead to activation of the inflammasome and subsequently cause secretion of IL-1β and IL-18. Thus, these actions may further aggravate the disease. On the other hand, some statins cause inhibition of the inflammasome or TLRs and along with lipid-lowering, help to improve the disease by reducing inflammation. In this article, we discuss these contradictory studies and the mechanisms of action of statins on the NLRP3 inflammasome and TLR pathways. The dose-dependent effects of statins on the NLRP3 complex are related to their chemistry, pharmacokinetic properties, and danger signals. Lipophilic statins have more pleiotropic effects on the NLRP3 complex in comparison to hydrophilic statins. Statins can suppress TLR4/MyD88/NF-ĸB signaling and cause an immune response shift to an anti-inflammatory response. Furthermore, statins inhibit the NF-ĸB pathway by decreasing the expression of TLRs 2 and 4. Statins are cost-effective drugs, which should have a continued future in the treatment of atherosclerosis due to both their immune-modulating and lipid-lowering effects.

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  1. [34]Galea J Armstrong J Gadsdon P Holden H Francis SE Holt CM Interleukin-1 beta in coronary arteries of patients with ischemic heart disease Arterioscler Thromb Vasc Biol 1996 16 8 1000 1006 8696938
  2. [57]Peter Stachon M, Adrian Heidenreich M, Ingo Hilgendorf M, Dennis Wolf M, Florian Willecke M, Sunaina von Garlen M, et al P2X7 deficiency blocks lesional inflammasome activity and ameliorates atherosclerosis in mice 28377486
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Authors
Koushki, K., Shahbaz, S. K., Mashayekhi, K., Sadeghi, M., Zayeri, Z. D., Taba, M. Y., Banach, M., Al-Rasadi, K., Johnston, T. P., & Sahebkar, A.
Affiliations
  • Mashhad University of Medical Sciences (IR)
  • Ahvaz Jundishapur University of Medical Sciences (IR)
  • Medical University of Lodz (PL)
  • University of Missouri–Kansas City (US)
Corresponding author
Sahebkar, Amirhossein
Venue
Clinical Reviews in Allergy & Immunology
Published
2020-05-06
Volume
60
Issue
2
Pages
175-199
ISSN
  • 1080-0549 (ISSN-L)
  • 1559-0267
OpenAlex
W3021399606
Cited by
382
References
216
Citations by year
2026: 50 · 2025: 74 · 2024: 70 · 2023: 86 · 2022: 52 · 2021: 40 · 2020: 9
FWCI
4.48
Type
journal article
Language
en
Open access
Locations
  • Clinical Reviews in Allergy & Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Polish Mother's Memorial Hospital Research Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
statins, atherosclerosis, NLRP3 inflammasome, Toll-like receptors, TLR4/MyD88/NF-κB signaling, IL-1β, IL-18, anti-inflammatory activity, hypolipidemic effect, dose-dependent effects, cardiovascular disease
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Anti-Inflammatory Agents, Cardiovascular Diseases, Humans, Signal Transduction, NF-kappa B, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Interleukin-18, Toll-Like Receptors, Interleukin-1beta, Inflammasomes

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