Cai Dunpeng, Chen Shi-You
Departments of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
The Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA.
Cells. 2025 Oct 14;14(20):1597. doi: 10.3390/cells14201597.
Abdominal aortic aneurysms (AAAs) are progressive, life-threatening vascular disorders characterized by focal dilation of the abdominal aorta due to chronic weakening of the arterial wall. The condition often remains asymptomatic until rupture, which carries mortality rates exceeding 70-85%. Among the various etiological theories of AAA development, degradation of the extracellular matrix (ECM) has emerged as the most widely accepted paradigm, with the breakdown of elastin representing a central and irreversible hallmark event. Elastin, a highly cross-linked and durable structural protein, provides elasticity and recoil to the aortic wall. In human AAA specimens, reduced elastin content, impaired cross-linking, and extensive fiber fragmentation are consistently observed, while experimental studies across multiple animal models confirm that elastin degradation directly correlates with aneurysm initiation, expansion, and rupture risk. Elastin loss is driven by a complex interplay of proteolytic enzymes coupled with inflammatory cell infiltration and oxidative stress. Furthermore, elastin-derived peptides perpetuate immune cell recruitment and matrix degradation, creating a vicious cycle of wall injury. Genetic and epigenetic factors, including variants in ECM regulators and dysregulation of non-coding RNAs, further modulate elastin homeostasis in AAA pathobiology. Clinically, biomarkers of elastin turnover and elastin-targeted molecular imaging techniques are emerging as tools for risk stratification. Therapeutically, novel strategies aimed at stabilizing elastin fibers, enhancing cross-linking, or delivering drugs directly to sites of elastin damage have shown promise in preclinical models and early translational studies. In parallel, regenerative approaches employing stem cells, exosomes, and bioengineered elastin scaffolds are under development to restore structural integrity. Collectively, these advances underscore the pivotal roles of elastin not only as a structural determinant of aneurysm development but also as a diagnostic and therapeutic target. This review summarizes and integrates recent discoveries on elastin biology in AAA, with a particular emphasis on molecular mechanisms of elastin degradation and the translational potential of elastin-centered interventions for the prevention and treatment of AAA.
腹主动脉瘤（AAAs）是一种渐进性、危及生命的血管疾病，其特征是由于动脉壁慢性薄弱导致腹主动脉局部扩张。这种疾病在破裂前通常没有症状，而破裂后的死亡率超过70%-85%。在腹主动脉瘤发展的各种病因理论中，细胞外基质（ECM）的降解已成为最被广泛接受的范式，其中弹性蛋白的分解是一个核心且不可逆转的标志性事件。弹性蛋白是一种高度交联且持久的结构蛋白，为主动脉壁提供弹性和回缩力。在人类腹主动脉瘤标本中，始终观察到弹性蛋白含量减少、交联受损和广泛的纤维断裂，而多项动物模型的实验研究证实，弹性蛋白降解与动脉瘤的起始、扩张和破裂风险直接相关。弹性蛋白的丢失是由蛋白水解酶、炎症细胞浸润和氧化应激的复杂相互作用驱动的。此外，弹性蛋白衍生的肽会持续招募免疫细胞并导致基质降解，从而形成壁损伤的恶性循环。遗传和表观遗传因素，包括ECM调节因子的变异和非编码RNA的失调，进一步调节腹主动脉瘤病理生物学中的弹性蛋白稳态。临床上，弹性蛋白周转的生物标志物和针对弹性蛋白的分子成像技术正在成为风险分层的工具。在治疗方面，旨在稳定弹性蛋白纤维、增强交联或直接将药物递送至弹性蛋白损伤部位的新策略在临床前模型和早期转化研究中已显示出前景。与此同时，采用干细胞、外泌体和生物工程弹性蛋白支架的再生方法正在开发中，以恢复结构完整性。总的来说，这些进展强调了弹性蛋白不仅作为动脉瘤发展的结构决定因素，而且作为诊断和治疗靶点的关键作用。本综述总结并整合了近期关于腹主动脉瘤中弹性蛋白生物学的发现，特别强调了弹性蛋白降解的分子机制以及以弹性蛋白为中心的干预措施在腹主动脉瘤预防和治疗中的转化潜力。
