Fig. 3.

Therapeutic approaches for VEDS have focused on addressing the aortic rupture. In particular β targeting adrenergic signalling via celiprolol, which has been used in clinical trials in Europe but failed FDA-approval and treatment in mice has given contrasting outcomes [51], [57]. Targeting MMP via doxycycline has also been used, while inhibition of PLC/IP₃/PKC/ERK reduced lethality and aortic rupture. Similarly, targeting androgen signalling was also effective. The cross talk between these pathways, how they are activated by either ECM defects and/or the impact of altered proteostasis, remains poorly defined (AR: androgen receptor, Hsp heat shock protein).