Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein.
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 conditionsin 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.
Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 10029, China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.|The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 10029, China.|Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing 10029, China.|Beijing Engineering Research Center for Vascular Prostheses, Beijing, China, 10029.
Wen-Jian
WJ
Jiang
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.
Wei-Hong
WH
Ren
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.
Xu-Jie
XJ
Liu
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.
Yan
Y
Liu
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.
Fu-Jian
FJ
Wu
Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.|The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 10029, China.|Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing 10029, China.|Beijing Engineering Research Center for Vascular Prostheses, Beijing, China, 10029.
Li-Zhong
LZ
Sun
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.
Feng
F
Lan
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.
Jie
J
Du
Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 10029, China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 10029, China.|Beijing Laboratory for Cardiovascular Precision Medicine, Beijing 10029, China.|The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 10029, China.|Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing 10029, China.|Beijing Engineering Research Center for Vascular Prostheses, Beijing, China, 10029.
Hong-Jia
HJ
Zhang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001011:Aorta / Q000378:metabolism* / Q000601:surgery; D001014:Aortic Aneurysm / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D017209:Apoptosis / Q000502:physiology; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
Stanford type A aortic dissection; extracellular matrix; mechanical stress; vascular smooth muscle cell; yes-associated protein