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イシグロ タイチ
ISHIGURO Taichi
石黒 太一 所属 医学部 医学科（附属八千代医療センター） 職種 准教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress. |
| 掲載誌名 | 正式名：Hypertension (Dallas, Tex. : 1979) 略 称：Hypertension ISSNコード：15244563/0194911X |
| 掲載区分 | 国外 |
| 巻・号・頁 | pp.1 |
| 著者・共著者 | Ishiguro Taichi, Furukawa Hajime, Polen Kyle, Take Yushiro, Sato Hiroki, Kudo Daisuke, Morgan Jordan, Uchikawa Hiroki, Maeda Takuma, Cisneros Oscar, Rahmani Redi, Ai Jinglu, Eguchi Satoru, Lawton Michael, Hashimoto Tomoki |
| 担当区分 | 筆頭著者 |
| 発行年月 | 2024/01 |
| 概要 | BACKGROUND:Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress.METHODS:Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture.RESULTS:Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture.CONCLUSIONS:Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage. |
| DOI | 10.1161/HYPERTENSIONAHA.123.21235 |
| PMID | 38164754 |