24-dehydrocholesterol reductase ameliorates senescence-related dysfunction of vascular endothelial cells
10.3760/cma.j.issn.0254-9026.2024.03.012
- VernacularTitle:24-脱氢胆固醇还原酶改善血管内皮细胞衰老相关功能障碍
- Author:
Han LI
1
;
Zhen YANG
;
Jinhua YAN
;
Le ZHANG
;
Cuntai ZHANG
;
Xiaoyan HUANG
Author Information
1. 华中科技大学同济医学院附属同济医院综合医疗科，武汉 430030
- Keywords:
Endothelium, Vascular;
Cell aging;
DHCR24;
Endothelial dysfunction
- From:
Chinese Journal of Geriatrics
2024;43(3):336-341
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of 24-dehydrocholesterol reductase(DHCR24)in doxorubicin-induced senescence-related dysfunction of vascular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were induced with 0.05 μM doxorubicin for 48 h to establish a stress-triggered premature senescence model.The lentiviral transfection method was employed to achieve DHCR24 overexpression in HUVECs.Cell senescence was evaluated by β-galactosidase staining and Western blot to detect the expression of the senescence-related molecules cyclin-dependent kinase inhibitor 1A(P21)and nicotinamide adenine dinucleotide dependent histone deacetylase 1(SIRT1).Western blot was performed to detect DHCR24 and endothelial nitric oxide synthase(eNOS)expression during endothelial senescence.DAF-FM DA(an NO fluorescent probe)was used to detect intracellular NO production.Results:In the stress-triggered premature senescence model of HUVECs induced by doxorubicin, the expression of the senescence marker P21 was up-regulated( t=19.44, P<0.01), SIRT1 was down-regulated( t=10.10, P<0.01, and the expression of DHCR24 was down-regulated( t=5.946, P<0.01), compared with the control group.Meanwhile, eNOS and NO expression was inhibited( t=11.26, P<0.01; t=10.83, P<0.01).After DHCR24 overexpression, compared with the control stimulation group, the overexpression stimulation group showed that DHCR24( F=72.10, P<0.01)was up-regulated.DHCR24 overexpression alleviated the doxorubicin-induced decrease in eNOS and NO( F=5.797, P<0.05; F=45.12, P<0.01), compared with the control group. Conclusions:DHCR24 may mitigate doxorubicin-induced senescence-related vascular endothelial dysfunction by modulating the eNOS/NO signaling pathway.
