| BACKGROUND: Cardiovascular and cerebrovascular diseases are a serious threat to human health and life globally.Atherosclerosis(AS)is the main cause of cardiovascular and cerebrovascular diseases.AS is a slowly progressive disease that starts from the intima and contains lipid deposits,fibrous tissue hyperplasia,and plaque formation,which ultimately leads to stenosis of the lumen.During the occurrence and development of AS,the medial vascular smooth muscle cells(VSMCs)of the arterial wall proliferate and migrate to the intima,and undergo a phenotypic change of VSMCs.Numerous studies have shown that the phenotype of VSMCs changes from contracted VSMCs to secreted VSMCs during the course of AS.Secretory VSMCs migrate to the inner membrane,abnormal proliferation occurs,and extracellular matrix(ECM)is secreted.The increase of ECM promotes the formation of AS plaques and participates in the hardening of the tube wall.Peroxiredoxin 2(PRDX2)can clear reactive oxygen species(ROS).It is a member of the peroxide reductase family.It is located in the cytoplasm and is extremely rich in red blood cells.PRDX2 regulates H2O2 concentration,signaling,oxidative stress,and cell repair in cells.ROS has a variety of biological activities and is a toxic molecule.It can participate in a variety of physiological and pathological processes by regulating mitogen-activated protein kinase(MAPK)signaling pathways,such as promoting cell proliferation,migration,and differentiation.,Apoptosis.A large number of studies show that the increase of ROS accelerates the occurrence and development of AS.The MAPK signaling pathway is involved in major physiological processes such as cell growth,differentiation,division,and apoptosis through the cytoskeleton,phosphorylated transcription factors,and enzymes,and has a significant correlation with tumors,inflammation and other diseases.It has been found in mammals that the MAPK signaling pathway is mainly composed of P38,JNK and ERK signaling pathways.Intercellular cell adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)are members of the Ig gene superfamily and are involved in regulating cell differentiation And development,inflammatory response,immune response,and tumor spread and metastasis.In the lesion area of ??AS,the expression of VCAM-1 and ICAM-1 was up-regulated.During the occurrence anddevelopment of AS,the expression of ROS,VCAM-1 and ICAM-1 increased,which accelerated the process of AS.To explore the role and mechanism of PRDX2 in the occurrence and development of AS can provide new strategies for the prevention and control of AS.Objective: To explore the role and mechanism of PRDX2 in the development of AS lesions.Methods: Human arterial specimens and vascular smooth muscle cells obtained from14 autopsies(7 AS,7 AS-free)were used as research objects.Real-time quantitative PCR,Western Bolt,immunohistochemistry,immunofluorescence,cell proliferation,and cells Migration,HE,EVG,cell transfection,reactive oxygen detection and other experimental methods to detect the proliferation and migration ability of smooth muscle cells,the transformation of cell phenotype,cell transfection,the location of gene expression,PRDX2,ROS,VCAM-1,The expressions of ICAM-1,COLⅠ,COLⅢ and P38,JNK and ERK signaling pathways were explored to explore the role of PRDX2 in the development of AS.In addition,through the use of P38,JNK and ERK pathway inhibitors,the mechanism of PRDX2 to promote / inhibit AS development was explored.Result:1.To detect the expression of PRDX2 in human carotid tissue,the protein and gene expression levels in the AS group were significantly higher than those in the normal group,and the expressions of ROS,VCAM-1,ICAM-1,COLⅠ,and COLⅢ proteins in the AS group were significantly higher than in the normal group.Increased amount,immunohistochemical localization showed that compared with normal tissues,PRDX2,OPN,SM22α were strongly positively expressed in smooth muscle cell envelope,and P38,JNK and ERK signaling pathways were abnormally activated when AS occurred.2.Tumor necrosis factor-alpha(TNF-α)induces human cervical smooth muscle cells,enhances the smooth muscle cell proliferation and migration ability,changes the smooth muscle cell phenotype,changes from contractive to secretory,PRDX2,ROS Compared with normal smooth muscle cells,the protein expression of VCAM-1,ICAM-1,COLⅠand COLⅢ significantly increased,and the P38,JNK and ERK signaling pathways were activated by tumor necrosis factor α.3.After si-PRDX2 acts on human cervical smooth muscle cells,smooth muscle cell proliferation and migration capabilities become stronger,the content of reactive oxygen species increases,P38,JNK,and ERK signaling pathways are activated,VCAM-1,ICAM-1,COLⅠ,and COLⅢ Compared with the normal group,the protein expression increased,which promoted the occurrence and development of AS.4.After PEX4-PRDX2 acts on TNF-α-induced smooth muscle cells,the protein expression of VCAM-1,ICAM-1,COLⅠ and COLⅢ is lower than that of TNF-α-induced smooth muscle cell proteome,and P38,JNK and ERK are reduced.The signal pathway is inhibited and the content of active oxygen is weakened,which suggests that the increase of PRDX2 can clear the active oxygen and inhibit the P38,JNK and ERK signal pathways,which can protect the development of AS.5.Pathway inhibitors act on si-PRDX2 to stimulate human cervical smooth muscle cells.Compared with si-PRDX2 on smooth muscle cells,the protein expression of VCAM-1and ICAM-1 is reduced,and the P38,JNK and ERK signaling pathways are reduced.It is inhibited,and it exerts biological effects through this in AS.Conclusion:1.PRDX2 inhibits the progression of AS by inhibiting the phenotype transition,proliferation,migration and ECM synthesis of VSMCs.2.PRDX2 inhibits the development of AS by inhibiting ROS and negatively regulating the MAPK signaling pathway. |
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