Naringenin promotes atherosclerotic palque stability by regulating the expression of TIMP-3 in smooth muscle cells
10.20039/j.cnki.1007-3949.2024.07.003
- VernacularTitle:柚皮素通过调控平滑肌细胞TIMP-3表达促进动脉粥样硬化斑块稳定
- Author:
Hui HE
1
;
Doudou DONG
;
Meng DING
;
Yuan ZHU
;
Tianyu JIANG
;
Xiaoting XU
;
Hailong OU
Author Information
1. 贵州医科大学基础医学院生物化学与分子生物学教研室,贵州省贵阳市 561113
- Keywords:
naringenin;
signal tansducer and activator of transcipion 6;
tissue inhibitor of metalloproteinase-3;
atherosclerosis;
plaque stability
- From:
Chinese Journal of Arteriosclerosis
2024;32(7):567-572,582
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effects of naringenin on atherosclerotic plaque extracellular matrix remodeling and plaque stability.Methods Murine vascular smooth muscle cells were isolated and treated with various doges of naringenin.ApoE-/-mice were fed with high-fat diet and received naringenin by lavage for 16 weeks.Intraplaque nec-rotic core,contents of collagen and fibrous cap thickness were measured by Sirius red-Haematoxylin staining.Elastin was detected by Van Gieson staining.Matrix metalloproteinase(MMP)activity was determined by gelatin zymography and fluorescence-gelatin staining.Results Naringenin(50 μmol/L)increased signal tansducer and activator of transciption 6(STAT6)phosphorylation and promoted tissue inhibitor of metalloproteinase-3(TIMP-3)expression by 3.1-fold(P＜0.001).After naringenin(80 mg/kg)treatment,compared with the control group,the area of plaque necrotic core in aor-tic root decreased by 53％(P＜0.01),the thickness of fibrous caps increased by nearly 50％(P＜0.05),and the degree of elastic fiber degradation decreased.At the same time,naringenin promoted the expression of TIMP-3 in plaques,and corre-spondingly reduced the activity of MMP in plaques.Lentivirus mediated inhibition of TIMP-3 expression in vivo could reduce the protective effect of naringenin on plaque stability.Conclusion Naringin can increase the expression of TIMP-3 in smooth muscle cells,improve the composition of extracellular matrix,and promote the stability of atherosclerotic plaque.
