Effects Of P53 On The Transdifferentiation Of Smooth Muscle Cells To Osteoblast-like Cells In Arterial Calcification

Objective: Vascular calcification is a common pathological manifestation in atherosclerosis,hypertension,vascular injury,diabetic vascular disease,chronic kidney disease and aging.Vascular smooth muscle cells play an important role in vascular calcification.The stromal vesicles released by VSMCs and the apoptotic bodies produced after apoptosis jointly initiate the calcification process.Calcification-related proteins,calcification-promoting substances,mi RNAs and osteogenic-related genes are related to the regulation of expression.They play an important regulatory role in the calcification of VSMCs and promote the transdifferentiation of VSMCs into bone-like cells.VSMCs undergo phenotypic changes in osteochondrocytes,and the expression of mineralization regulatory proteins is up-regulated which leads to vascular calcification.Previous studies have found that p53 mediates the transformation and differentiation process of fibroblasts,endothelial cells,and cardiomyocytes.Therefore,we boldly speculate that p53 is closely related to the regulation of VSMC osteogenic phenotype transformation in vascular calcification.To this end,we need to verify whether downregulation of p53 protein expression in arteriosclerotic lesions can inhibit the process of VSMC osteogenic phenotype transformation.Materials and Methods :We randomly selected 21 male apo E-/-mice about 6-8 weeks old and fed them on a high-fat diet for 12 weeks.They were randomly divided into three groups: control group,parthenolide injection group,and pifithrin/-u injection group.The method of administration is intraperitoneal injection,once every other day.After 4 weeks of administration,the mice were anesthetized to obtain materials,and the left common carotid artery and part of the thoracic aorta were fixed in vitro.The embedded sections of the left common carotid artery were stained with Alizarin Red,HE staining and thoracic aorta oil Red O staining.In vitro experiments were performed on primary vascular smooth muscle cells of rats.High-phosphorus and high-sugar medium was used to induce cell calcification.After 14 days of induction,the cells were given parthenolide and pifithrin/-u drugs.After 12 hours,the protein was extracted,and Western blot was used to detect the expression of p53,AC-p53,MSX2 and other proteins related to atherosclerosis.Results: After analyzing the experimental results,the following conclusions are drawn:1 In animal experiments,oil red O staining of the thoracic aorta showed that p53 inhibitors reduced the area of atherosclerotic plaques;Alizarin red staining showed that p53 inhibitors reduced vascular luminal stenosis;HE staining showed that p53 inhibitors inhibited arterial intimal hyperplasia;Vascular ring experiment shows that p53 inhibitors improve thoracic aortic vascular function.2 In cell experiments,we found that p53 inhibitors down-regulate the expression of BMP2,MSX2,PREP protein in calcified smooth muscle cells and promote the expression of BMPR1 A protein which is related to the down-regulation of P-p53/p53 expression.Conclusion:1 p53 inhibitors can reduce the area of atherosclerotic plaques,reduce vascular lumen stenosis,inhibit arterial intimal hyperplasia,and improve the vascular function of the thoracic aorta.2 p53 inhibitors down-regulate the expression of BMP2,MSX2,PREP protein in calcified smooth muscle cells and promote the expression of BMPR1 A protein which is related to the down-regulation of P-p53/p53 expression.