TRIM13 reduces cholesterol efflux and increases oxidized LDL uptake leading to foam cell formation and atherosclerosis.

Autor:	Govatati S; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Kumar R; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Boro M; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Traylor JG Jr; Department of Pathology, Louisiana State University Health Science Center, Shreveport, Louisiana, USA., Orr AW; Department of Pathology, Louisiana State University Health Science Center, Shreveport, Louisiana, USA., Lusis AJ; Division of Cardiology, Department of Medicine, University of California, Los Angeles, California, USA., Rao GN; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. Electronic address: rgadipar@uthsc.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 May; Vol. 300 (5), pp. 107224. Date of Electronic Publication: 2024 Mar 25.
DOI:	10.1016/j.jbc.2024.107224
Abstrakt:	Impaired cholesterol efflux and/or uptake can influence arterial lipid accumulation leading to atherosclerosis. Here, we report that tripartite motif-containing protein 13 (TRIM13), a RING-type E3 ubiquitin ligase, plays a role in arterial lipid accumulation leading to atherosclerosis. Using molecular approaches and KO mouse model, we found that TRIM13 expression was induced both in the aorta and peritoneal macrophages (pMφ) of ApoE -/- mice in response to Western diet (WD) in vivo. Furthermore, proatherogenic cytokine interleukin-1β also induced TRIM13 expression both in pMφ and vascular smooth muscle cells. Furthermore, we found that TRIM13 via ubiquitination and degradation of liver X receptor (LXR)α/β downregulates the expression of their target genes ABCA1/G1 and thereby inhibits cholesterol efflux. In addition, TRIM13 by ubiquitinating and degrading suppressor of cytokine signaling 1/3 (SOCS1/3) mediates signal transducer and activator of transcription 1 (STAT1) activation, CD36 expression, and foam cell formation. In line with these observations, genetic deletion of TRIM13 by rescuing cholesterol efflux and inhibiting foam cell formation protects against diet-induced atherosclerosis. We also found that while TRIM13 and CD36 levels were increased, LXRα/β, ABCA1/G1, and SOCS3 levels were decreased both in Mφ and smooth muscle cells of stenotic human coronary arteries as compared to nonstenotic arteries. More intriguingly, the expression levels of TRIM13 and its downstream signaling molecules were correlated with the severity of stenotic lesions. Together, these observations reveal for the first time that TRIM13 plays a crucial role in diet-induced atherosclerosis, and that it could be a potential drug target against this vascular lesion. Competing Interests: Conflict of interest The authors declare that they have no conflict of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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