Research Paper Volume 8, Issue 9 pp 1923—1939
Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein
- 1 Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 10029, China
- 2 Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China
- 3 Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China
- 4 The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 10029, China
- 5 Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing 10029, China
- 6 Beijing Engineering Research Center for Vascular Prostheses, Beijing, China, 10029
Received: June 11, 2016 Accepted: September 6, 2016 Published: September 5, 2016
https://doi.org/10.18632/aging.101033How to Cite
Abstract
In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro, and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome.