Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis

• DOI: 10.3389/fcell.2021.651579
• Publication Date: 2021-05-06T05:25:05Z
• Authors: Yingzhen Zhang; Xiaoli Yang; Zhongzhong Li; Kailin Bu; Tong Li; Zhizhao Ma; Binbin Wang; Lina Ma; Honglin Lu; Kun Zhang; Luji Liu; Yanying Zhao; Yipu Zhu; Jin Qin; Junzhao Cui; Lin Liu; Shuxia Liu; Ping Fan; Xiaoyun Liu
• Keywords: 0301 basic medicine; Cell and Developmental Biology; 03 medical and health sciences; QH301-705.5; Pyk2/MCU; ApoE–/– mice; mitochondrion; atherosclerosis; Biology (General); HUVECs

Objective: Multiple mechanisms including vascular endothelial cell damage have a critical role in the formation and development of atherosclerosis (AS), but specific molecular are not exactly clarified. This study aims to determine possible roles proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway AS mouse model H O -induced explore its mechanisms. Approach Results: The was established using apolipoprotein E-knockout (ApoE –/– ) mice that were fed with high-fat diet. It very interesting find Pyk2/MCU expression significantly increased artery wall atherosclerotic human umbilical vein cells (HUVECs) attacked by hydrogen peroxide (H ). In addition, down-regulation Pyk2 short hairpin RNA (shRNA) protected HUVECs from insult. Furthermore, treatment rosuvastatin on HUVEC injury showed protective effect against inhibiting pathway, which maintained balance, prevented mitochondrial reactive oxygen species production, eventually inhibited apoptosis. Conclusion: Our results provide important insight into initiation involved AS-related damage, may be new promising target for intervention.