Sestrin2 increases in aortas and plasma from aortic dissection patients and alleviates angiotensin II-induced smooth muscle cell apoptosis via the Nrf2 pathway.

Background: Previous studies have demonstrated that oxidative stress is closely related to aortic dissection (AD). Sestrin2 (Sesn2) is an important antioxidant protein, and this study aimed to investigate whether Sesn2 participates in AD and the possible mechanisms.

Methods: Sesn2 expression was detected in aortas collected from AD patients and normal donors. In addition, blood samples were collected from AD patients and non-AD (NAD) patients, and the plasma Sesn2 levels were measured. Furthermore, the effects of Sesn2 on angiotensin (Ang) II-induced smooth muscle cell (SMC) apoptosis were investigated in vitro.

Results: Compared with the aortas from normal donors, aortas from AD patients had significantly increased Sesn2. Sesn2 was mainly secreted by macrophages, and low levels were secreted by CD4+ T lymphocytes, but not SMCs. Plasma Sesn2 levels were also increased in AD patients compared with NAD patients. Sesn2 levels were negatively corrected with superoxide dismutase (SOD) levels but positively corrected with malondialdehyde (MDA) levels in AD patients. In co-cultures of macrophages and SMCs, Sesn2 overexpression in macrophages significantly reduced Ang II-induced SMC apoptosis, and this effect could be reversed by Nrf2 silencing.

Conclusions: Sesn2 is increased in both aortas and plasma from AD patients. Sesn2 may alleviate Ang II-induced SMC apoptosis and participate in AD via the Nrf2 pathway. Sesn2 may be a new target in the treatment and prevention of AD.