Proteomic study of the microdissected aortic media in human thoracic aortic aneurysms.
Aortic aneurysm is a complex multifactorial disease, and its molecular mechanism is not understood. In thoracic aortic aneurysm (TAA), the expansion of the aortic wall is lead by extracellular matrix (ECM) degeneration in the medial layer, which leads to weakening of the aortic wall. This dilatation may end in rupture and-if untreated-death. The aortic media is composed of vascular smooth muscle cells (VSMCs) and proteins involved in aortic elasticity and distensibility. Delineating their functional and quantitative decrease is critical in elucidating the disease causing mechanisms as well as the development of new preventive therapies. Laser microdissection (LMD) is an advanced technology that enables the isolation of the desired portion of tissue or cells for proteomics analysis, while preserving their integrity. In our study, the aortic media layers of 36 TAA patients and 8 controls were dissected using LMD technology. The proteins isolated from these tissue samples were subjected to comparative proteomic analysis by nano-LC-MS/MS, which enabled the identification of 352 proteins in aortic media. Among these, 41 proteins were differentially expressed in the TAA group with respect to control group, and all were downregulated in the patients. Of these medial proteins, 25 are novel, and their association with TAA is reported for the first time in our study. Subsequent analysis of the data by ingenuity pathway analysis (IPA) shows that the majority of differentially expressed proteins were found to be cytoskeletal-associated proteins and components of the ECM which are critical in maintaining aortic integrity. Our results indicate that the protein expression profile in the aortic media from TAA patients differs significantly from controls. Further analysis of the mechanism points to markers of pathological ECM remodeling, which, in turn, affect VSMC cytosolic structure and architecture. In the future, the detailed investigation of the differentially expressed proteins may provide insight into the elucidation of the pathological processes underlying aneurysms.
['Serhatli|Muge|M|', 'Baysal|Kemal|K|', 'Acilan|Ceyda|C|', 'Tuncer|Eylem|E|', 'Bekpinar|Seldag|S|', 'Baykal|Ahmet Tarik|AT|']
D000328:Adult D000368:Aged D001011:Aorta D017545:Aortic Aneurysm, Thoracic D016022:Case-Control Studies D003598:Cytoskeletal Proteins D005109:Extracellular Matrix D016326:Extracellular Matrix Proteins D005260:Female D006801:Humans D007834:Lasers D008297:Male D042282:Microdissection D008875:Middle Aged D009131:Muscle, Smooth, Vascular D011506:Proteins D040901:Proteomics D053719:Tandem Mass Spectrometry
thoracic aortic aneurysm vascular smooth muscle protein expression label-free proteomics laser capture microdissection