From the Department of Vascular Surgery, Leiden University Medical Center, the Netherlands (J.H.L.).
Division of Vascular Surgery, School of Medicine and Public Health, University of Wisconsin, Madison (J.S.M.).
Circ Res. 2019 Feb 15;124(4):631-646. doi: 10.1161/CIRCRESAHA.118.312439.
Current management of aortic aneurysms relies exclusively on prophylactic operative repair of larger aneurysms. Great potential exists for successful medical therapy that halts or reduces aneurysm progression and hence alleviates or postpones the need for surgical repair. Preclinical studies in the context of abdominal aortic aneurysm identified hundreds of candidate strategies for stabilization, and data from preoperative clinical intervention studies show that interventions in the pathways of the activated inflammatory and proteolytic cascades in enlarging abdominal aortic aneurysm are feasible. Similarly, the concept of pharmaceutical aorta stabilization in Marfan syndrome is supported by a wealth of promising studies in the murine models of Marfan syndrome-related aortapathy. Although some clinical studies report successful medical stabilization of growing aortic aneurysms and aortic root stabilization in Marfan syndrome, these claims are not consistently confirmed in larger and controlled studies. Consequently, no medical therapy can be recommended for the stabilization of aortic aneurysms. The discrepancy between preclinical successes and clinical trial failures implies shortcomings in the available models of aneurysm disease and perhaps incomplete understanding of the pathological processes involved in later stages of aortic aneurysm progression. Preclinical models more reflective of human pathophysiology, identification of biomarkers to predict severity of disease progression, and improved design of clinical trials may more rapidly advance the opportunities in this important field.
目前,主动脉瘤的治疗主要依赖于对较大动脉瘤进行预防性手术修复。通过医学治疗来阻止或减缓动脉瘤的进展,从而减轻或推迟手术修复的需求,具有巨大的潜力。在腹主动脉瘤的临床前研究中,已经确定了数百种稳定动脉瘤的候选策略,而且术前临床干预研究的数据表明,干预不断扩大的腹主动脉瘤中激活的炎症和蛋白水解级联途径是可行的。同样,在马凡综合征相关的主动脉病变的鼠模型中,大量有前景的研究也支持了药物稳定主动脉的概念。尽管一些临床研究报告了成功的医学稳定生长的主动脉瘤和马凡综合征中的主动脉根部稳定,但在更大规模和对照研究中,这些结果并未得到一致证实。因此,目前还没有推荐用于稳定主动脉瘤的医学治疗方法。临床前的成功和临床试验的失败之间的差异表明,现有的动脉瘤疾病模型存在缺陷,或者对主动脉瘤进展后期涉及的病理过程的理解还不完全。更能反映人类病理生理学的临床前模型、识别预测疾病进展严重程度的生物标志物以及改进临床试验设计,可能会使该重要领域的研究进展更快。