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Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways
Open accessAbstract
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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“In addition to their primary role in lowering LDL cholesterol, statins have demonstrated potential in various off‐label applications, such as anti‐inflammatory and immunomodulatory effects, which continue to drive research into their expanded therapeutic uses [108, 109].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [108]
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“These drugs have exhibited other pleiotropic effects; antioxidant, anticoagulant (Vadivoo et al. 2018), anticancer (Gupta et al. 2019; Di Bello et al. 2020); anti-inflammatory (Koushki et al. 2021) and antibacterial activities (Ko et al. 2017; Vadivoo et al. 2018”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Koushki et al. 2021
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Metadata
- 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
- ORCID
- Venue
- Clinical Reviews in Allergy & Immunology
- Published
- 2020-05-06
- Volume
- 60
- Issue
- 2
- Pages
- 175-199
- ISSN
- 1080-0549 (ISSN-L)
- 1559-0267
- PMC
- PMC7985098
- 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
- hybrid
- doi.org
- 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 › Cardiology and Cardiovascular Medicine › 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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