IMR Press / FBL / Volume 25 / Issue 2 / DOI: 10.2741/4807

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Simvastatin improves lysosome function via enhancing lysosome biogenesis in endothelial cells
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1 School of Pharmacy, Hubei University of Science and Technology, Xianning, China
2 Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204
Send correspondence to: Xiang Li, Department of Pharmacological & Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5056, Tel: 7137437978, Fax: 7137431259, E-mail: 33TUxli61@central.uh.eduU33T
Front. Biosci. (Landmark Ed) 2020, 25(2), 283–298; https://doi.org/10.2741/4807
Published: 1 January 2020
(This article belongs to the Special Issue Inflammasomes in cardiovascular diseases)
Abstract

Nlrp3 inflammasomes were shown to play a critical role in triggering obesity-associated early onsets of cardiovascular complications such as endothelial barrier dysfunction with endothelial hyperpermeability. Statins prevent endothelial dysfunction and decrease cardiovascular risk in patients with obesity and diabetes. However, it remains unclear whether statin treatment for obesity-induced endothelial barrier dysfunction is in part due to the blockade of Nlrp3 inflammasome signaling axis. The results showed that simvastatin, a clinically and widely used statin, prevented free fatty acid-induced endothelial hyperpermeability and disruption of ZO-1 and VE-cadherin junctions in mouse microvascular endothelial cells (MVECs). This protective effect of simvastatin was largely due to improved lysosome function that attenuated lysosome injury-mediated Nlrp3 inflammasome activation and subsequent release of high mobility group box protein-1 (HMGB1). Mechanistically, simvastatin induces autophagy that promotes removal of damaged lysosomes and also promotes lysosome regeneration that preserves lysosome function. Collectively, simvastatin treatment improves lysosome function via enhancing lysosome biogenesis and its autophagic turnover, which may be an important mechanism to suppress Nlrp3 inflammasome activation and prevents endothelial hyperpermeability in obesity.

Keywords
Free Fatty Acid
Inflammasome
Statin
Lysosome
Autophagy
Endothelial Hyperpermeability
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