Research ArticleVASCULAR BIOLOGY

TFEB inhibits endothelial cell inflammation and reduces atherosclerosis

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Sci. Signal.  31 Jan 2017:
Vol. 10, Issue 464,
DOI: 10.1126/scisignal.aah4214

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Protected from atherosclerosis by TFEB

Atherosclerosis, or the buildup of fatty plaques in blood vessels, can lead to high blood pressure and heart attacks. Lu et al. found that, in cultured endothelial cells, the transcription factor TFEB reduced oxidative stress and inflammation, two processes thought to contribute to the development of atherosclerosis. When fed a high-fat diet, mice that overexpressed TFEB in endothelial cells developed smaller atherosclerotic lesions than their control littermates on the same diet. Thus, treatments that enhance the activity of TFEB in endothelial cells could reduce the development of atherosclerosis. Furthermore, because the anti-inflammatory effect of TFEB in endothelial cells was independent of its role in autophagy, a process in which cells digest macromolecules and organelles, these results highlight new roles for this transcription factor.

Abstract

Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis. We investigated the function of TFEB in vascular biology and pathophysiology and demonstrated that TFEB in endothelial cells inhibited inflammation and reduced atherosclerosis development. Laminar shear stress, which protects against atherosclerosis, increased TFEB abundance in cultured primary human endothelial cells. Furthermore, TFEB overexpression in these cells was anti-inflammatory, whereas TFEB knockdown aggravated inflammation. The anti-inflammatory effect of TFEB was, at least, partially due to reduced oxidative stress because TFEB overexpression in endothelial cells decreased the concentrations of reactive oxygen species and increased the expression of the antioxidant genes HO1 (which encodes heme oxygenase 1) and SOD2 (which encodes superoxide dismutase 2). In addition, transgenic mice with endothelial cell–specific expression of TFEB exhibited reduced leukocyte recruitment to endothelial cells and decreased atherosclerosis development. Our study suggests that TFEB is a protective transcription factor against endothelial cell inflammation and a potential target for treating atherosclerosis and associated cardiovascular diseases.

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