Liver X Receptor Agonist Inhibits Oxidized Low-Density Lipoprotein Induced Choroidal Neovascularization via the NF-κB Signaling Pathway

Autor: Tong Wu, Xinli Wei, Kuanrong Dang, Mengzhang Tao, Baozhen Lv, Tao Chen, Zuoming Zhang, Jian Zhou, Hongjun Du
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Medicine
Volume 12
Issue 4
Pages: 1674
ISSN: 2077-0383
DOI: 10.3390/jcm12041674
Popis: Age-related macular degeneration (AMD) is the most common blindness-causing disease among the elderly. Under oxidative stress, low-density lipoprotein in the outer layer of the retina is easily converted into oxidized low-density lipoprotein (OxLDL), which promotes the development of choroidal neovascularization (CNV), the main pathological change in wet AMD. Liver X receptor (LXR), a ligand-activated nuclear transcription factor, regulates various processes related to CNV, including lipid metabolism, cholesterol transport, inflammation, and angiogenesis. In this study, we evaluated the effects of the LXR agonist TO901317 (TO) on CNV. Our results demonstrated that the TO could inhibit OxLDL-induced CNV in mice as well as inflammation and angiogenesis in vitro. Using siRNA transfection in cells and Vldlr−/− mice, we further confirmed the inhibitory effects of TO against the inflammatory response and oxidative stress. Mechanistically, the LXR agonist reduces the inflammatory response via the nuclear translocation of NF-κB p65 in the pathway for NF-κB activation and by enhancing ABCG1-dependent lipid transportation. Therefore, an LXR agonist is a promising therapeutic candidate for AMD, especially for wet AMD.
Databáze: OpenAIRE
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