Effects of Vericiguat on ox-LDL-induced Endothelial Dysfunction and Mitophagy
DENG Xinling
WANG Miaoqian
LI Shaojie
MA Mingfeng
Abstract：Objective:To explore the protective effect of vericiguat on ox-LDL-induced endothelial dysfunction and its underlying mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were divided into three groups:the control group received no intervention,the ox-LDL group was treated with ox-LDL for 24 hours,the vericiguat group was treated with ox-LDL for 24 hours and then intervened with vericiguat for another 24 hours.CCK-8 was used to detect cell viability.Transwell assays were used to assess cell migration.Lactate dehydrogenase release assays were used to evaluate cell damage.Nitrate reductase assays were used to measure nitric oxide levels.The DCFH-DA fluorescent probe was used to detect intracellular reactive oxygen species(ROS).The superoxide dismutase(SOD)levels in the cell culture supernatant were measured using a kit.Mitochondrial autophagy-related proteins tensin homolog induced putative kinase 1(PINK1),Parkin,microtubule-associated protein light chain 3 Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ),and p62 were detected by Western Blot.The real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression of mitochondrial autophagy-related genes LC3 and p62.Results:ox-LDL significantly reduced the viability and mobility of HUVECs,increased LDH leakage,enhanced ROS production,and weakened intracellular SOD activity,whereas vericiguat could reverse these effects.ox-LDL could up-regulate the expression of mitochondrial autophagy molecules,including PINK1,Parkin,LC3Ⅱ/Ⅰ,and p62 protein,as well as LC3 and p62 mRNA.Vericiguat could further up-regulate the protein expression of mitochondrial autophagy molecules such as PINK1,Parkin,and LC3Ⅱ/Ⅰ,while down-regulate the expression of p62 protein and mRNA.Conclusion:Vericiguat can improve ox-LDL-induced endothelial cell dysfunction and reduce oxidative stress to some extent,and improvment of mitochondrial autophagic flux disorder is possible.
Keywords：endothelial dysfunctionvericiguatoxidized low-density lipoproteinoxidative stressmitophagyexperimental study
Publication Date：2026-02-25
Online Publishing Date：2026-03-16(First online date of this platform, not the publication date of the document)
Pages：7( 539-545 )