AUTHOR=Zhang Yingzhen , Yang Xiaoli , Li Zhongzhong , Bu Kailin , Li Tong , Ma Zhizhao , Wang Binbin , Ma Lina , Lu Honglin , Zhang Kun , Liu Luji , Zhao Yanying , Zhu Yipu , Qin Jin , Cui Junzhao , Liu Lin , Liu Shuxia , Fan Ping , Liu Xiaoyun 

TITLE=Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.651579

DOI=10.3389/fcell.2021.651579

ISSN=2296-634X

ABSTRACT=Objective: Multiple mechanisms including vascular endothelial cells damage have a critical role in the formation and development of atherosclerosis (AS), but the specific molecular mechanisms are not exactly clarified. This study aims to determine the possible roles of proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway in AS mouse model and H2O2-induced endothelial cells damage model and explore its possible mechanisms.
Approach and Results: AS mouse model was established using apolipoprotein E-knockout (ApoE−/−) mice that were fed with high fat diet. It was very interesting to find that Pyk2/MCU expression was significantly increased in the artery wall of atherosclerotic mice and human umbilical vein endothelial cells (HUVECs) attacked by H2O2. In addition, down-regulation of Pyk2 by short hairpin RNA (shRNA) protected HUVECs from H2O2 insult. Furthermore, treatment with the rosuvastatin on AS mouse model and H2O2-induced HUVECs injury model showed a protective effect against AS by inhibiting Pyk2/MCU pathway, which maintained calcium balance, prevented the mitochondrial damage, reactive oxygen species (ROS) production, and eventually inhibited cell apoptosis.
Conclusions: Our results provide important insight into the initiation of Pyk2/MCU pathway involved in AS related ECs damage, which may be a new promising target for atherosclerosis intervention.