Chuyang Tai, Cong Ling, Yang Yang, Ni Mo, Cian Yao, Songtian Lv, Baoyu Zhang, Hui Wang, Chuan Chen
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引用次数: 0
Abstract
Aims: This study aimed to investigate the specific mechanism by which angiopoietin-2 (ANGPT2)/Tie2 signaling in macrophages promotes endothelial cell (EC) proliferation in the chronically ischaemic brain (CIB).
Methods: We first analyzed the polarization status of primary Tie2-expressing macrophages (TEMs) and Tie2-overexpressing THP-1-derived macrophages (Tie2-TDMs) following ANGPT2 treatment and detected the expression of representative proangiogenic factors. Subsequently, lysine lactylation (Kla) levels were measured, and chromatin immunoprecipitation (ChIP) assays were performed to explore the downstream activity of ANGPT2/Tie2 signaling. Additionally, in vitro functional assays using human umbilical vein endothelial cells (HUVECs) and in vivo experiments in a rat model of chronic cerebral ischaemia were conducted to confirm the effect of ANGPT2/Tie2-regulated macrophages on angiogenesis.
Results: In response to ANGPT2 treatment, the expression of M2 polarization markers and proangiogenic factors increased in TEMs and Tie2-TDMs. Concurrently, LDHA and H3K18la were elevated, and ChIP assays confirmed the regulatory role of ANGPT2/Tie2 signaling in H3K18la-mediated transcriptional regulation. The viability of HUVECs cocultured with Tie2-TDMs was increased. Finally, ANGPT2 overexpression increased M2-polarized TEM infiltration in the CIB; additionally, rats injected with ANGPT2-pretreated TEMs exhibited more prominent EC proliferation.
Conclusion: ANGPT2/Tie2 induces the H3K18la-mediated M2 polarization of macrophages to facilitate EC proliferation and angiogenesis in the CIB.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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