期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1868, 期 5, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbalip.2022.159258
关键词
Atherosclerosis; Endothelial activation; Adhesion; Inflammation; Tumor necrosis factor (TNF)
Atherosclerosis, a chronic inflammatory condition linked to cardiovascular diseases, is a global public health concern. This study found that USP14, a deubiquitinating enzyme, is downregulated in atherosclerosis patients and stimulated endothelial cells. Overexpression of USP14 inhibits endothelial proinflammatory activation by suppressing NF-xB activation and adhesion molecule production. In vivo experiments confirmed that USP14 adenovirus injection in mice reduced atherosclerotic lesions and restricted disease progression.
Atherosclerosis, a chronic inflammatory condition that leads to a variety of life-threatening cardiovascular diseases, is a worldwide public health concern. Endothelial cells (ECs), which line the inside of blood vessels, play an important role in atherogenic initiation. Endothelial activation and inflammation are indispensable for the early stage of atherosclerosis. Ubiquitin-specific protease 14 (USP14), a deubiquitinating enzyme that reg-ulates the stability and activity of target proteins, has been identified as a potential therapeutic target for many inflammatory diseases. However, the role of USP14 on ECs is undefined. In this study, we found that USP14 is downregulated in either atherosclerosis patient specimens or oxidized low-density lipoprotein (ox-LDL)-stimu-lated ECs as compared to the control group. Overexpression of USP14 in ECs restrains ox-LDL-stimulated nuclear transcription factor kappa B (NF-xB) activation and subsequent adhesion molecule production. USP14 inhibits endothelium proinflammatory activation by suppressing the degradation of the negative regulator of NF-xB signaling, nod-like receptor family caspase recruitment domain family domain containing 5 (NLRC5). Finally, our in vivo experiments confirmed that USP14 adenovirus injection in apolipoprotein E deficient (ApoE-/-) mice fed with a western diet reduced the atherosclerotic lesion size, inhibited macrophage accumulation in the intima, and restricted the progression of atherosclerosis. Our results reveal that USP14 may represent a new therapeutic target for atherosclerosis.
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