RT Journal Article
SR Electronic
T1 Androgen aggravates aortic aneurysms via suppressing PD-1 in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.22.525073
DO 10.1101/2023.01.22.525073
A1 Mu, Xufang
A1 Liu, Shu
A1 Wang, Zhuoran
A1 Jiang, Kai
A1 McClintock, Tim
A1 Stromberg, Arnold J.
A1 Tezanos, Alejandro V.
A1 Lee, Eugene S
A1 Curci, John A.
A1 Gong, Ming C
A1 Guo, Zhenheng
YR 2023
UL http://biorxiv.org/content/early/2023/01/22/2023.01.22.525073.abstract
AB Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms, a devastating vascular disease with a higher prevalence and mortality rate in men than women. However, the molecular mechanism by which androgen mediates aortic aneurysms is largely unknown. Here, we report that male but not female mice develop aortic aneurysms in response to aldosterone and high salt (Aldo-salt). We demonstrate that both androgen and androgen receptors (AR) are crucial for the sexually dimorphic response to Aldo-salt. We identify T cells expressing programmed cell death protein 1 (PD-1), an immune checkpoint molecule important in immunity and cancer immunotherapy, as a key link between androgen and aortic aneurysms. We show that intraperitoneal injection of anti-PD-1 antibody reinstates Aldo-salt-induced aortic aneurysms in orchiectomized mice. Mechanistically, we demonstrate that AR binds to the PD-1 promoter to suppress its expression in the spleen. Hence, our study reveals an important but unexplored mechanism by which androgen contributes to aortic aneurysms by suppressing PD-1 expression in T cells. Our study also suggests that cancer patients predisposed to the risk factors of aortic aneurysms may be advised to screen for aortic aneurysms during immune checkpoint therapy.Competing Interest StatementThe authors have declared no competing interest.