Statins Suppress Apolipoprotein CIII-Induced Vascular Endothelial Cell Activation and Monocyte Adhesion

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Statins Suppress Apolipoprotein CIII-Induced Vascular Endothelial Cell Activation and Monocyte Adhesion

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Title: Statins Suppress Apolipoprotein CIII-Induced Vascular Endothelial Cell Activation and Monocyte Adhesion
Author: Zheng, Chunyu; Azcutia, Veronica; Aikawa, Elena; Figueiredo, Jose-Luiz; Croce, Kevin James; Sonoki, Hiroyuki; Sacks, Frank Martin; Luscinskas, Francis William; Aikawa, Masanori

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Citation: Zheng, Chunyu, Veronica Azcutia, Elena Aikawa, Jose-Luiz Figueiredo, Kevin James Croce, Hiroyuki Sonoki, Frank Martin Sacks, Francis William Luscinskas, and Masanori Aikawa. 2012. Statins suppress apolipoprotein CIII-induced vascular endothelial cell activation and monocyte adhesion. European Heart Journal 34(8): 615-624.
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Abstract: Aims: Activation of vascular endothelial cells (ECs) contributes importantly to inflammation and atherogenesis. We previously reported that apolipoprotein CIII (apoCIII), found abundantly on circulating triglyceride-rich lipoproteins, enhances adhesion of human monocytes to ECs in vitro. Statins may exert lipid-independent anti-inflammatory effects. The present study examined whether statins suppress apoCIII-induced EC activation in vitro and in vivo. Methods and results: Physiologically relevant concentrations of purified human apoCIII enhanced attachment of the monocyte-like cell line THP-1 to human saphenous vein ECs (HSVECs) or human coronary artery ECs (HCAECs) under both static and laminar shear stress conditions. This process mainly depends on vascular cell adhesion molecule-1 (VCAM-1), as a blocking VCAM-1 antibody abolished apoCIII-induced monocyte adhesion. ApoCIII significantly increased VCAM-1 expression in HSVECs and HCAECs. Pre-treatment with statins suppressed apoCIII-induced VCAM-1 expression and monocyte adhesion, with two lipophilic statins (pitavastatin and atorvastatin) exhibiting inhibitory effects at lower concentration than those of hydrophilic pravastatin. Nuclear factor κB (NF-κB) mediated apoCIII-induced VCAM-1 expression, as demonstrated via loss-of-function experiments, and pitavastatin treatment suppressed NF-κB activation. Furthermore, in the aorta of hypercholesterolaemic \(Ldlr^{−/−}\) mice, pitavastatin administration in vivo suppressed VCAM-1 mRNA and protein, induced by apoCIII bolus injection. Similarly, in a subcutaneous dorsal air pouch mouse model of leucocyte recruitment, apoCIII injection induced F4/80+ monocyte and macrophage accumulation, whereas pitavastatin administration reduced this effect. Conclusions: These findings further establish the direct role of apoCIII in atherogenesis and suggest that anti-inflammatory effects of statins could improve vascular disease in the population with elevated plasma apoCIII.
Published Version: doi:10.1093/eurheartj/ehs271
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578265/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10613658
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