High glutamine increases stroke risk by inducing the endothelial‐to‐mesenchymal transition in moyamoya disease

Autor: Qiheng He, Junsheng Li, Chuming Tao, Chaofan Zeng, Chenglong Liu, Zhiyao Zheng, Siqi Mou, Wei Liu, Bojian Zhang, Xiaofan Yu, Yuanren Zhai, Jia Wang, Qian Zhang, Yan Zhang, Dong Zhang, Jizong Zhao, Peicong Ge
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: MedComm, Vol 5, Iss 5, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2688-2663
11918411
DOI: 10.1002/mco2.525
Popis: Abstract At present, there is limited research on the mechanisms underlying moyamoya disease (MMD). Herein, we aimed to determine the role of glutamine in MMD pathogenesis, and 360 adult patients were prospectively enrolled. Human brain microvascular endothelial cells (HBMECs) were subjected to Integrin Subunit Beta 4 (ITGB4) overexpression or knockdown and atorvastatin. We assessed factors associated with various signaling pathways in the context of the endothelial‐to‐mesenchymal transition (EndMT), and the expression level of related proteins was validated in the superficial temporal arteries of patients. We found glutamine levels were positively associated with a greater risk of stroke (OR = 1.599, p = 0.022). After treatment with glutamine, HBMECs exhibited enhanced proliferation, migration, and EndMT, all reversed by ITGB4 knockdown. In ITGB4‐transfected HBMECs, the MAPK–ERK–TGF–β/BMP pathway was activated, with Smad4 knockdown reversing the EndMT. Furthermore, atorvastatin suppressed the EndMT by inhibiting Smad1/5 phosphorylation and promoting Smad4 ubiquitination in ITGB4‐transfected HBMECs. We also found the protein level of ITGB4 was upregulated in the superficial temporal arteries of patients with MMD. In conclusion, our study suggests that glutamine may be an independent risk factor for hemorrhage or infarction in patients with MMD and targeting ITGB4 could potentially be therapeutic approaches for MMD.
Databáze: Directory of Open Access Journals
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