@article{Shi2025, 
author = {Yi Shi and Hao-Min Chen and Ai-Hua Liu and Xiao-Rong Li},
title = {Fenofibrate mitigates the dysfunction of high glucose-driven human retinal microvascular endothelial cells by suppressing NLRP3 inflammasome},
year = {2025},
journal = {International Journal of Ophthalmology},
volume = {18},
number = {5},
pages = {792-801},
keywords = {fenofibrate, human retinal microvascular endothelial cells, high glucose, NOD-like receptor thermal protein domain associated protein 3 inflammasomes, oxidative stress},
url = {https://www.sciopen.com/article/10.18240/ijo.2025.05.04},
doi = {10.18240/ijo.2025.05.04},
abstract = {AIMTo determine the therapeutic benefits of fenofibrate (Feno) on the dysfunction of high glucose (HG)-induced human retinal microvascular endothelial cells (HRMECs) and to elucidate the underlying molecular mechanism.METHODSHRMEC dysfunction model was established by 48h glucose (30 mmol/L) treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activator (Nigericin). Cell viability/apoptosis were assessed by cell counting kit-8 (CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining and flow cytometry assays. Levels of apoptosis- (Bcl-2-associated X protein, Bax/B-cell lymphoma 2, Bcl-2), vascular permeability-(vascular endothelial growth factor, VEGF) and inflammasome activation-related proteins (NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD, ASC), as well as inflammatory factors (interleukin, IL-6/IL-1β/tumor necrosis factor, TNF-α/IL-18) were determined with Western blot/enzyme linked immunosorbent assay (ELISA). Cell permeability/reactive oxygen species (ROS) level/superoxide dismutase (SOD) activity/malondialdehyde (MDA) content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe/SOD kit/MDA kit.RESULTSHRMEC dysfunction was successfully induced by HG, evidenced by decreased viability (P<0.001), increased apoptosis (P<0.001), permeability (P<0.001), and inflammatory factor levels (P<0.001). Feno treatment significantly ameliorated HG-induced HRMEC dysfunction (P<0.01). Meanwhile, HG induction increased ROS production (P<0.001) and MDA content (P<0.001) in HRMECs, while reducing SOD activity (P<0.001), indicative of oxidative stress. This was, however, abolished by Feno (P<0.05). Moreover, Feno eliminated activation of NLRP3 inflammasomes (P<0.05) in HG-induced HRMECs. Strikingly, activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction (P<0.05).CONCLUSIONFeno represses oxidative stress and NLRP3 inflammasome activation, consequently alleviating HG-induced HRMEC dysfunction.}
}