Comparative tissue proteomics analysis of thoracic aortic dissection with hypertension using the iTRAQ technique.
OBJECTIVE
To identify differentially expressed proteins from the aortic tissue of thoracic aortic dissection (TAD) with hypertension and normal aorta and to explore the potential molecular pathogenesis of TAD.


METHODS
Aortic tissue samples were collected from two groups of age- and gender-matched patients with TAD and normal aorta. These samples were subjected to isobaric tags for relative and absolute quantitation analysis to identify the proteins involved in TAD. Signalling pathways were analysed using the Metacore software, and the identified proteins were validated by western blotting.


RESULTS
A total of 36 proteins were identified between two groups, with 19 of them being significantly down-regulated and 17 up-regulated in patients with TAD. Proteins including fibrillin-1, emilin-1, decorin, protein DJ-1 and histone H4 were validated by western blotting. The enrichment analysis performed using the Metacore process networks data showed that cell adhesion_cell-matrix interactions, proteolysis_extracellular matrix (ECM) remodelling and inflammation_interleukin 6 (IL-6) signalling were the main protein interaction networks involved in TAD. We further observed indications of increased transforming growth factor-β (TGF-β) signalling and impaired aortic wall remodelling, both of which may be molecular mechanisms for the pathogenesis of TAD.


CONCLUSIONS
The differentially expressed proteins identified in our study are mainly involved in cell-matrix interaction, ECM remodelling and inflammation. These mechanisms, combined with the TGF-β signalling pathway, may play an important role in the pathogenesis of TAD.
Department of Cardiovascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Kefeng
K
Zhang
Beijing Aortic Disease Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Xudong
X
Pan
Beijing Aortic Disease Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Jun
J
Zheng
Department of Cardiovascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Dong
D
Xu
Department of Cardiovascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China lancetzkf@aliyun.com.
Jian
J
Zhang
Beijing Aortic Disease Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Lizhong
L
Sun
D000784:Aortic Dissection / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000378:metabolism; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta
D020543:Proteome; D016212:Transforming Growth Factor beta
Proteomics; Thoracic aortic dissection; iTRAQ