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The effect of low-dose proteasome inhibition on pre-existing atherosclerosis in LDL receptor-deficient mice

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Item Type:Article
Title:The effect of low-dose proteasome inhibition on pre-existing atherosclerosis in LDL receptor-deficient mice
Creators Name:Wilck, N. and Fechner, M. and Dan, C. and Stangl, V. and Stangl, K. and Ludwig, A.
Abstract:Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in atherosclerosis development. However, the nature of UPS dysfunction has been proposed to be specific to certain stages of atherosclerosis development, which has implications for proteasome inhibition as a potential treatment option. Recently, low-dose proteasome inhibition with bortezomib has been shown to attenuate early atherosclerosis in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice. The present study investigates the effect of low-dose proteasome inhibition with bortezomib on pre-existing advanced atherosclerosis in LDLR(-/-) mice. We found that bortezomib treatment of LDLR(-/-) mice with pre-existing atherosclerosis does not alter lesion burden. Additionally, macrophage infiltration of aortic root plaques, total plasma cholesterol levels, and pro-inflammatory serum markers were not influenced by bortezomib. However, plaques of bortezomib-treated mice exhibited larger necrotic core areas and a significant thinning of the fibrous cap, indicating a more unstable plaque phenotype. Taking recent studies on favorable effects of proteasome inhibition in early atherogenesis into consideration, our data support the hypothesis of stage-dependent effects of proteasome inhibition in atherosclerosis.
Keywords:Atherosclerosis, Proteasome Inhibition, Inflammation, Animals, Mice
Source:International Journal of Molecular Sciences
ISSN:1422-0067
Publisher:MDPI (Switzerland)
Volume:18
Number:4
Page Range:781
Date:7 April 2017
Official Publication:https://doi.org/10.3390/ijms18040781
PubMed:View item in PubMed

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