Simvastatin Suppresses Interleukin Iβ Release in Human Peripheral Blood Mononuclear Cells Stimulated With Cholesterol Crystals

Journal of Cardiovascular Pharmacology and Therapeutics
Anna J BolandMargaret Lucitt

Abstract

Statins are mainstream therapy in the treatment and prevention of cardiovascular disease through inhibitory effects on cholesterol synthesis. However, statins' beneficial effects in cardiovascular disease may also be attributable to their role as anti-inflammatory mediators. Here, we investigated the effects of simvastatin treatment on expression levels of interleukin (IL) 1β in both patient with hyperlipidemia and healthy human peripheral blood mononuclear cells (PBMCs) using cholesterol crystals (CC), a cardiovascular pathogenic stimulus for activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Cholesterol crystal-induced NLRP3 inflammasome activation was used to trigger maturation and release of IL-1β in PBMCs. Specifically, isolated PBMCs from patients with hyperlipidemia at baseline and following 8 weeks of in vivo treatment with simvastatin (10-20 mg) daily were stimulated with lipopolysaccharide (LPS; 100 ng/mL) for 3 hours to induce proIL-Iβ expression followed by CC (2 mg/mL) stimulation for further 18 hours to activate the NLRP3 inflammasome complex to induce maturation/activation of IL-1β. Peripheral blood mononuclear cells were also isolated from healthy donors and stimulated in...Continue Reading

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Citations

Apr 25, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Yang LiuYunlun Li
May 8, 2020·Clinical Reviews in Allergy & Immunology·Khadijeh KoushkiAmirhossein Sahebkar
Jun 21, 2020·British Journal of Pharmacology·Raul R Rodrigues-DiezMarta Ruiz-Ortega
Jul 16, 2020·Biomedicines·Anastasia V PoznyakAlexander N Orekhov
Nov 20, 2020·Lasers in Medical Science·Luana Gabriel de SouzaRafael Inácio Barbosa
Jul 6, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Qun WangGaofeng Zeng
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Biswadeep DasAkash Agnihotri
Oct 1, 2021·Advanced Biology·Yvonne BaumerWilliam A Boisvert

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay

Software Mentioned

KC Junior
Graph Pad
Graph Pad Prism

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