S-propargyl-cysteine delays the progression of atherosclerosis and increases eNOS phosphorylation in endothelial cells.
- Author:
Zhi-Ming LI
1
;
Ping LI
1
;
Lei ZHU
2
;
Yu-Wen ZHANG
3
;
Yi-Chun ZHU
1
;
He WANG
3
;
Bo YU
2
;
Ming-Jie WANG
4
Author Information
1. Shanghai Key Laboratory of Bioactive Small Molecules, the Innovative Research Team of High-Level Local Universities in Shanghai, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
2. Department of Vascular Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
3. Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.
4. Shanghai Key Laboratory of Bioactive Small Molecules, the Innovative Research Team of High-Level Local Universities in Shanghai, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. mjwang@shmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Humans;
Mice;
Atherosclerosis;
Cholesterol/metabolism*;
Cysteine/pharmacology*;
Human Umbilical Vein Endothelial Cells/metabolism*;
Lipoproteins, LDL/pharmacology*;
Nitric Oxide Synthase Type III/metabolism*;
Phosphorylation;
Plaque, Atherosclerotic/pathology*
- From:
Acta Physiologica Sinica
2023;75(3):317-327
- CountryChina
- Language:English
-
Abstract:
The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.
