Qiumei Zhang, Qian Zhu, Yongjie Zhang, Nan Li
Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Human Anatomy, Nanjing Medical University, Nanjing, China; State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Human Anatomy, Nanjing Medical University, Nanjing, China.
Life Sci. 2025 Oct 1;378:123829. doi: 10.1016/j.lfs.2025.123829. Epub 2025 Jul 1.
Cardiovascular diseases with their related secondary complications are the main causes of morbidity and mortality worldwide. Abdominal aortic aneurysm (AAA) belongs to the cardiovascular diseases and causes approximately 1.3 % of all deaths among men between 65 and 85 years old in developed countries [1]. The pathogenesis of AAA mainly attributes to pathological dilation of the abdominal aorta, which will further lead to a high mortality rate up to 85 % due to excessive dilation and rupture [2]. A criterion was proposed in 1991 that AAA infrarenal aorta diameter should be 1.5 times the normal diameter [3], and McGregor additionally defined AAA as an aorta with a diameter greater than 30 mm in the infrarenal segment [4]. Although the diagnosis of AAA seems conclusive, there is no specific treatment to prevent AAA expansion. Elective aortic repair operation is conditional recommended when the aneurysm diameter reaches 55 mm in men, 50 mm in women or grows by 6 mm to 8 mm per year [5]. However, small aneurysms probably also grow rapidly or rupture at a high risk, and even some patients die from aneurysm rupture before they manifest surgical indications. Thus, controlling risk factors and exploring novel therapeutic approaches gradually substitute as key directions for aneurysm treatment. Smoking, hypertension, age and gender have been identified as the common risk factors during AAA progression in the past decades [6], but the mechanisms how these hazards contribute to pathological dilatation of abdominal aortas remain unclear. Interestingly, histone modifications have recently emerged as an important link between the intrinsic genetic landscape and extrinsic risk factors, and a plethora of studies have been dedicated to exploring the role of histone modifications in AAA pathogenesis. In this review, current progress on the contribution of histone modifications to the regulation of AAA will be summarized.
心血管疾病及其相关的继发性并发症是全球发病和死亡的主要原因。腹主动脉瘤(AAA)属于心血管疾病,在发达国家65至85岁的男性中,约占所有死亡人数的1.3%[1]。AAA的发病机制主要归因于腹主动脉的病理性扩张,由于过度扩张和破裂,这将进一步导致高达85%的高死亡率[2]。1991年提出了一个标准,即AAA肾下主动脉直径应为正常直径的1.5倍[3],McGregor还将AAA定义为肾下段直径大于30mm的主动脉[4]。尽管AAA的诊断似乎确凿无疑,但尚无预防AAA扩张的特异性治疗方法。当男性动脉瘤直径达到55mm、女性达到50mm或每年增长6至8mm时,有条件地建议进行选择性主动脉修复手术[5]。然而,小动脉瘤也可能迅速生长或破裂,风险很高,甚至一些患者在出现手术指征之前就死于动脉瘤破裂。因此,控制危险因素和探索新的治疗方法逐渐成为动脉瘤治疗的关键方向。在过去几十年中,吸烟、高血压、年龄和性别已被确定为AAA进展过程中的常见危险因素[6],但这些危险因素如何导致腹主动脉病理性扩张的机制仍不清楚。有趣的是,组蛋白修饰最近已成为内在遗传格局与外在危险因素之间的重要联系,并且大量研究致力于探索组蛋白修饰在AAA发病机制中的作用。在本综述中,将总结组蛋白修饰对AAA调控作用的当前进展。