Functional damage of endothelial progenitor cells is attenuated by 14‐3‐3‐n through inhibition of mitochondrial injury and oxidative stress

Abstract

Endothelial progenitor cells (EPCs) are precursor cells of vascular endothelial cells, which are widely involved in the pathological process of cardiovascular diseases. EPCs apoptosis could accelerate the process of cardiovascular diseases. 14-3-3-η protein has been proved to be a potent antiapoptosis molecule. However, inhibition of EPCs apoptosis by 14-3-3-η and further specific mechanism have not been investigated. EPCs were isolated from human cord blood, and identified using VEGFR2 and CD34. 14-3-3-η overexpression model in vitro was established. Cell invasion, apoptosis, and proliferation were measured by transwell, flow cytometry, and Cell Counting Kit-8, respectively. Expression of 14-3-3-η, Bcl-2, and voltagedependent anion channel 1 (VDAC1) were measured using quantitative real-time polymerase chain reaction and western blot analysis. Reactive oxygen species (ROS) intensity was measured using 2ʹ-7ʹ dichlorofluorescin diacetate probe. Mitochondrial membrane potential was detected using JC-1 dye. Overexpression of 14-3-3-η significantly promoted invasion and proliferation, but suppressed apoptosis of EPCs. Overexpression of 14-3-3-η remarkably inhibited ROS and promoted antioxidant enzyme levels in EPCs. 14-3-3-η might inhibit apoptosis of EPCs through attenuating mitochondrial injury. This study might provide a new target, 14-3-3-η, for the prevention and treatment of cardiovascular diseases through targeting EPCs.

14‐3‐3‐η interacts with BCL‐2 to protect human endothelial progenitor cells from ox‐LDL‐triggered damage

“…Among 14‐3‐3 family members, 14‐3‐3‐η has been reported to be a diagnostic marker for rheumatoid arthritis (RA) (Maksymowych, Naides, et al, 2014, Maksymowych, van der Heijde, et al, 2014), but its precise function in RA and other biological processes is not well defined. Recently, we reported that 14‐3‐3‐η overexpression can inhibit ox‐LDL‐induced apoptosis and oxidative stress in EPCs (Li et al, 2021), and a similar finding was also reported in mouse cardiomyocytes (Sreedhar et al, 2015). However, the mechanism by which 14‐3‐3‐η antagonizes the effect of ox‐LDL on EPCs remains unknown.…”

“…The isolation of EPC was carried out as previously described (Li et al, 2021). In brief, 30 mL cord blood was collected from each full-term healthy parturient woman and was subjected to density gradient centrifugation to isolate mononuclear cells, which were plated into fibronectin-coated six-well culture plates at a density of 5 × 10 5 cells/cm 2 .…”

Effect of Danhong injection on heart failure in rats evaluated by metabolomics

“…The makers were entered into MetaboAnalyst to determine the impacted metabolism related pathways. 1 The Data analysis method is consistent with the previous publication ( 16 ).…”

“…Network pharmacology analysis and experimental validation also showed that DHI attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis ( 15 ). Furthermore, its ability to improve cardiac function, reduce myocardial injury, and enhance vascular endothelial function has been reported in both animal and clinical studies ( 8 , 16 ).…”