1. ADAMTS-5 Decreases in Aortas and Plasma From Aortic Dissection Patients and Alleviates Angiotensin II-Induced Smooth Muscle-Cell Apoptosis
- Author
-
Jianting Gan, Zhengde Lu, Lei Shi, Yu Liu, Tao Zeng, Yan Xue, Yingzhong Lin, Rixin Xiong, Ling Liu, Zicong Yang, and Jun Yuan
- Subjects
0301 basic medicine ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,matrix metalloproteinase ,extracellular matrix ,Cardiovascular Medicine ,030204 cardiovascular system & hematology ,Matrix metalloproteinase ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Renin–angiotensin system ,medicine ,Original Research ,Aortic dissection ,Thrombospondin ,Metalloproteinase ,acute aortic dissection ,business.industry ,ADAMTS ,apoptosis ,ADAMTS-5 ,medicine.disease ,Angiotensin II ,smooth muscle cells ,030104 developmental biology ,Endocrinology ,lcsh:RC666-701 ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Acute aortic dissection (AAD) is associated with degeneration of the aortic media and accompanied by vascular extracellular matrix (ECM) remodeling. Recently, a disintegrin and metalloproteinase with thrombospondin type 1 motifs-5 (ADAMTS-5) has been reported to be involved in ECM remodeling and vascular diseases. The aim of this study was to examine ADAMTS-5 levels in AAD patients and investigate the underlying mechanisms. Methods: Aortic tissue samples were collected from normal donors and AAD patients, and the expression of ADAMTS-5 was analyzed in all aortic tissues. In addition, plasma levels of ADAMTS-5, matrix metalloproteinase (MMP)-2 and MMP-9, and tumor necrosis factor-α (TNF-α) were measured in repeated samples from AAD patients and compared to the non-AAD (NAD) group. In addition, we investigated the effects of ADAMTS-5 in smooth muscle cell (SMC) apoptosis. Results: The results showed that ADAMTS-5 expression was significantly reduced in the aortas of AAD patients and that SMCs were the main source of ADAMTS-5. In addition, the plasma ADAMTS-5 level was lower, but plasma MMP-2, MMP-9, and TNF-α levels were increased in the AAD patients. Multivariate linear regression analyses showed that a decreased ADAMTS-5 level in patients was independently associated with an increased risk of AAD. Furthermore, recombinant human ADAMTS-5 significantly ameliorated angiotensin (Ang II)-evoked SMC apoptosis. Conclusions: ADAMTS-5 shows promise as a novel potential biomarker for AAD, and regulation of SMC is a possible mechanism for the effects of ADAMTS-5.
- Published
- 2020
- Full Text
- View/download PDF