Involvement of p53, p21, and Caspase-3 in Apoptosis of Coronary Artery Smooth Muscle Cells in a Kawasaki Vasculitis Mouse Model
Minghong Deng, Chunwang Lin, Xianglin Zeng, Jianping Zhang, Fang Wen, Ziguang Liu, Haiyan Wu, Xiaofeng Wu
Pediatric Intensive Care Unit, Shunde Women and Children’s Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland)
Med Sci Monit 2020; 26:e922429
Available online: 2020-06-20
Overexpression of p53, p21, and caspase-3 promotes apoptosis of vascular smooth muscle cells. However, the mechanisms that lead to apoptosis of coronary artery smooth muscle cells (CASMCs) is unclear in Kawasaki disease (KD). This study investigated involvement of p53, p21, and caspase-3 in the apoptosis of CASMCs from a Kawasaki vasculitis mouse model.
MATERIAL AND METHODS: The Kawasaki vasculitis mouse model with coronary artery lesions was generated via administration of Lactobacillus casei cell wall extract. In 2 groups of mice (healthy control and KD vasculitis mice), the levels of p53, p21, and caspase-3 protein in the root of the coronary artery were evaluated via immunohistochemistry. Receiver operating characteristic curves were plotted for determination of area under the curve, 95% confidence interval, sensitivity, specificity, and cutoff values for the ability of p53, p21, and caspase-3 expression to predict CASMC apoptosis and coronary artery lesion formation in KD vasculitis mice.
RESULTS: Compared with healthy mice, KD vasculitis mice had a significantly higher apoptosis index and upregulated p53, p21, and caspase-3 expression. Also, the immunoreactive score for caspase-3 was positively correlated with the immunoreactivity scores for p53 and p21. The optimal cutoff values for p53, p21, and caspase-3 expression for predicting the presence of coronary artery lesions were 4.15, 4.18, and 4.22, respectively.
CONCLUSIONS: Upregulated levels of p53, p21, and caspase-3 promoted apoptosis of CASMCs in KD vasculitis mice. Thus, the levels of p53, p21, and caspase-3 may serve as valuable predictors of coronary artery lesion formation in KD.
Keywords: Coronary Vessels, Apoptosis, Mucocutaneous Lymph Node Syndrome