Research Paper Volume 11, Issue 11 pp 3574—3584
TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome
- 1 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China
- 2 Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
- 3 Clinical Translational Medical Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
received: April 15, 2019 ; accepted: May 24, 2019 ; published: May 30, 2019 ;https://doi.org/10.18632/aging.101998
How to Cite
Copyright: You et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Formation of aortic aneurysms as a consequence of augmented transforming growth factor β (TGF-β) signaling and vascular smooth muscle cell (VSMC) dysfunction is a potentially lethal complication of Marfan syndrome (MFS). Here, we examined VSMC senescence in patients with MFS and explored the potential mechanisms that link VSMC senescence and TGF-β. Tissue was harvested from the ascending aorta of control donors and MFS patients, and VSMCs were isolated. Senescence-associated β-galactosidase (SA-β-gal) activity and expression of senescence-related proteins (p53, p21) were significantly higher in aneurysmal tissue from MFS patients than in healthy aortic tissue from control donors. Compared to control-VSMCs, MFS-VSMCs were larger with higher levels of both SA-β-gal activity and mitochondrial reactive oxygen species (ROS). In addition, TGF-β1 levels were much higher in MFS- than control-VSMCs. TGF-β1 induced VSMC senescence through excessive ROS generation. This effect was suppressed by Mito-tempo, a mitochondria-targeted antioxidant, or SC-514, a NF-κB inhibitor. This suggests TGF-β1 induces VSMC senescence through ROS-mediated activation of NF-κB signaling. It thus appears that a TGF-β1/ROS/NF-κB axis may mediate VSMC senescence and aneurysm formation in MFS patients. This finding could serve as the basis for a novel strategy for treating aortic aneurysm in MFS.