Aoki Tomohiro, Kayahara Tomomichi, Ono Isao, Okada Akihiro
Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center.
No Shinkei Geka. 2022 Jan;50(1):179-195. doi: 10.11477/mf.1436204543.
Genetic studies on intracranial aneurysms(IAs), like genome-wide association studies, or studies analyzing familial intracranial aneurysms, have successfully revealed the potential contribution of a set of genes to the pathology of IAs. Some of the genes may promote the formation of IAs or the process leading to rupture of the lesions through exacerbating inflammatory responses or facilitating the degenerative changes of arterial walls. Many genes or single-nucleotide polymorphisms have been identified through extensive analyses, but they can only explain one-fifth of the IA pathology; therefore, the pathogenesis of IAs is influenced by many factors, including environmental factors, and not only genetic ones. Intriguingly, a somatic mutation in the gene has recently been identified in more than half of the cases with fusiform aneurysms, making the development of medical therapy targeting PDGFRβ signaling realistic. Nowadays, following a series of recent experimental studies, IA is considered a chronic inflammatory disease affecting intracranial arteries, indicating the potential of anti-inflammatory drugs as therapeutic drugs for the treatment of IAs. No wonder, recently published observational studies have revealed the preventive effect of statins and aspirin, with potent anti-inflammatory effects on the rupture of IAs.
对颅内动脉瘤（IA）的遗传学研究，如全基因组关联研究或分析家族性颅内动脉瘤的研究，已成功揭示了一组基因对IA病理学的潜在作用。其中一些基因可能通过加剧炎症反应或促进动脉壁的退行性变化，从而促进IA的形成或导致病变破裂的过程。通过广泛分析已鉴定出许多基因或单核苷酸多态性，但它们只能解释五分之一的IA病理学；因此，IA的发病机制受多种因素影响，包括环境因素，而不仅仅是遗传因素。有趣的是，最近在超过一半的梭形动脉瘤病例中发现了该基因的体细胞突变，这使得针对血小板衍生生长因子受体β（PDGFRβ）信号通路的药物治疗成为现实。如今，经过一系列近期的实验研究，IA被认为是一种影响颅内动脉的慢性炎症性疾病，这表明抗炎药物作为IA治疗药物具有潜力。难怪最近发表的观察性研究揭示了他汀类药物和阿司匹林对IA破裂具有预防作用，它们具有强大的抗炎作用。
