2. Academic Validation
  3. Activated TREM1-mediated MAPK signaling in endothelial cells caused by highly expressed STAT1 is associated with intracranial aneurysms occurrence and rupture

Activated TREM1-mediated MAPK signaling in endothelial cells caused by highly expressed STAT1 is associated with intracranial aneurysms occurrence and rupture

  • Mol Cell Biochem. 2024 Dec 11. doi: 10.1007/s11010-024-05173-z.
Hao Zhu 1 2,  Ge Gao 2,  Yingang Wu 2,  Yang Wang 2,  Yu Chen 2,  Chaoshi Niu 3 4
Affiliations

Affiliations

  • 1 Cheeloo College of Medicine, Shandong University, No.44 Wenhua West Road, Lixia District, Jinan, 250012, China.
  • 2 Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No.1 Swan Lake Road, Hefei, 230001, China.
  • 3 Cheeloo College of Medicine, Shandong University, No.44 Wenhua West Road, Lixia District, Jinan, 250012, China. niuchaoshi@126.com.
  • 4 Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No.1 Swan Lake Road, Hefei, 230001, China. niuchaoshi@126.com.
PMID: 39661286 DOI: 10.1007/s11010-024-05173-z
Abstract

Intracranial aneurysm (IA) poses significant health risks, yet the specific mRNA profiles and regulatory mechanisms distinguishing unruptured IA (UIA) from ruptured IA (RIA) remain unclear. This study aimed to elucidate these differences through comprehensive mRNA analysis. We employed RNA Sequencing to compare mRNA expression patterns among control individuals, UIA patients, and RIA patients. Differential expression analysis identified triggering receptor expressed on myeloid cells 1 (TREM1) as a potential biomarker for IA occurrence and rupture, which was validated in an expanded cohort. In vitro experiments revealed that TREM1 overexpression in human umbilical vein endothelial cells (HUVECs) inhibited proliferation, angiogenesis, and migration while promoting Apoptosis and inflammation. Bioinformatic predictions and subsequent chromatin immunoprecipitation assays confirmed signal transducer and activator of transcription 1 (STAT1) as a transcriptional regulator of TREM1. STAT1 overexpression in HUVECs activated the MAPK signaling pathway and mimicked the effects of TREM1 overexpression, which were reversible by TREM1 inhibition. Conversely, p38 MAPK inhibition produced opposite effects, which were negated by STAT1 overexpression. This study identifies TREM1 as a potential biomarker for IA occurrence and rupture, likely regulated by STAT1, offering new avenues for non-invasive IA intervention strategies.

Keywords

Intracranial aneurysm; STAT1; TREM1; Transcriptional regulation.

Figures
Products