Transforming Growth Factor-β and the Renin-Angiotensin System in Syndromic Thoracic Aortic Aneurysms: Implications for Treatment

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-beta (TGF-beta) 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 beta-blockers in patients suffering from syndromic TAAs. This review highlights the contribution of TGF-beta 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 beta-blockers in syndromic TAA patients and provides future research perspectives and therapeutic implications.

Automated summary

Thoracic aortic aneurysms (TAAs) are permanent pathological dilatations of the thoracic aorta that can lead to life-threatening complications, frequently occurring in individuals with genetic predispositions such as Marfan syndrome and Loeys-Dietz syndrome. Research indicates the significant role of TGF-beta signaling and the renin-angiotensin system in the pathology of TAAs, with ongoing studies exploring the therapeutic potential of ARBs and beta-blockers in syndromic TAA patients.