Potential enhancement of post-stroke angiogenic response by targeting the oligomeric aggregation of p53 protein

Hoi Hei Tam; Dongxing Zhu; Samuel Sze King Ho; Heng Wai Vong; Vincent Kam Wai Wong; Simon Wing-Fai Mok; Io Nam Wong

doi:10.3389/fncel.2023.1193362

Potential enhancement of post-stroke angiogenic response by targeting the oligomeric aggregation of p53 protein

Front Cell Neurosci. 2023 Jul 18:17:1193362. doi: 10.3389/fncel.2023.1193362. eCollection 2023.

Authors

Hoi Hei Tam¹, Dongxing Zhu², Samuel Sze King Ho¹, Heng Wai Vong¹, Vincent Kam Wai Wong³, Simon Wing-Fai Mok^{1

3}, Io Nam Wong^{1

3}

Affiliations

¹ Faculty of Medicine, Macau University of Science and Technology, Macau, Macau SAR, China.
² Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Institute of Cardiovascular Disease, Guangzhou Medical University, Guangzhou, Guangdong, China.
³ Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, China.

Abstract

Tumor suppressor gene p53 and its aggregate have been found to be involved in many angiogenesis-related pathways. We explored the possible p53 aggregation formation mechanisms commonly occur after ischemic stroke, such as hypoxia and the presence of reactive oxygen species (ROS). The angiogenic pathways involving p53 mainly occur in nucleus or cytoplasm, with one exception that occurs in mitochondria. Considering the high mitochondrial density in brain and endothelial cells, we proposed that the cyclophilin D (CypD)-dependent vascular endothelial cell (VECs) necrosis pathway occurring in the mitochondria is one of the major factors that affects angiogenesis. Hence, targeting p53 aggregation, a key intermediate in the pathway, could be an alternative therapeutic target for post-stroke management.

Keywords: CypD; angiogenesis; p53; post-stroke recovery; protein aggregation.

Publication types

Review

Grants and funding

This project was financially supported by the MUST Faculty Research Grants (No. FRG-22-022-FMD) and the Macao Science and Technology Development Fund (Nos. 0069/2021/AFJ and 0037/2022/ITP).