TY - JOUR
T1 - Anti-inflammatory Action of Statins in Cardiovascular Disease
T2 - the Role of Inflammasome and Toll-Like Receptor Pathways
AU - Koushki, Khadijeh
AU - Shahbaz, Sanaz Keshavarz
AU - Mashayekhi, Kazem
AU - Sadeghi, Mahvash
AU - Zayeri, Zeinab Deris
AU - Taba, Mahdieh Yousefi
AU - Banach, Maciej
AU - Al-Rasadi, Khalid
AU - Johnston, Thomas P.
AU - Sahebkar, Amirhossein
N1 - Funding Information:
Dr. Banach has served on the speaker’s bureau and as an advisory board member for Amgen, Sanofi, Aventis, and Lilly. Dr. Al-Rasadi received research grant from Sanofi, served on the speaker’s bureau and as an advisory board member for Sanofi, Astra Zeneca and Pfizer. Other authors have no conflict of interests.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Cardiovascular disease
KW - Inflammasome
KW - NLRP3
KW - Statins
KW - TLR2
KW - TLR4
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U2 - 10.1007/s12016-020-08791-9
DO - 10.1007/s12016-020-08791-9
M3 - Review article
C2 - 32378144
AN - SCOPUS:85084481484
SN - 1080-0549
VL - 60
SP - 175
EP - 199
JO - Clinical Reviews in Allergy and Immunology
JF - Clinical Reviews in Allergy and Immunology
IS - 2
ER -