Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Cardiovasc Drugs Ther. 2021 Dec;35(6):1233-1252. doi: 10.1007/s10557-020-07116-4. Epub 2020 Dec 7.
Thoracic aortic aneurysms (TAAs) are permanent pathological dilatations of the thoracic aorta, which can lead to life-threatening complications, such as aortic dissection and rupture. TAAs frequently occur in a syndromic form in individuals with an underlying genetic predisposition, such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Increasing evidence supports an important role for transforming growth factor-β (TGF-β) and the renin-angiotensin system (RAS) in TAA pathology. Eventually, most patients with syndromic TAAs require surgical intervention, as the ability of present medical treatment to attenuate aneurysm growth is limited. Therefore, more effective medical treatment options are urgently needed. Numerous clinical trials investigated the therapeutic potential of angiotensin receptor blockers (ARBs) and β-blockers in patients suffering from syndromic TAAs. This review highlights the contribution of TGF-β signaling, RAS, and impaired mechanosensing abilities of aortic VSMCs in TAA formation. Furthermore, it critically discusses the most recent clinical evidence regarding the possible therapeutic benefit of ARBs and β-blockers in syndromic TAA patients and provides future research perspectives and therapeutic implications.
胸主动脉瘤（TAAs）是胸主动脉的永久性病理性扩张，可导致危及生命的并发症，如主动脉夹层和破裂。TAAs 在具有潜在遗传易感性的个体中常以综合征形式出现，如马凡综合征（MFS）和洛伊茨-迪茨综合征（LDS）。越来越多的证据支持转化生长因子-β（TGF-β）和肾素-血管紧张素系统（RAS）在 TAA 病理学中的重要作用。最终，大多数综合征性 TAA 患者需要手术干预，因为目前的药物治疗减缓动脉瘤生长的能力有限。因此，迫切需要更有效的治疗方法。许多临床试验研究了血管紧张素受体阻滞剂（ARBs）和β受体阻滞剂在综合征性 TAA 患者中的治疗潜力。这篇综述强调了 TGF-β信号、RAS 和主动脉平滑肌细胞机械敏感性受损在 TAA 形成中的作用。此外，还批判性地讨论了 ARBs 和β受体阻滞剂在综合征性 TAA 患者中可能的治疗益处的最新临床证据，并提供了未来的研究前景和治疗意义。
