title: Proteomic study of the microdissected aortic media in human thoracic aortic aneurysms.
abstract: 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.
authors.affiliation: TUBITAK-Marmara Research Center, Genetic Engineering and Biotechnology Institute , 41470 Gebze, Kocaeli, Turkey.
authors.forename: Muge
authors.initials: M
authors.lastname: Serhatli
authors.forename: Kemal
authors.initials: K
authors.lastname: Baysal
authors.forename: Ceyda
authors.initials: C
authors.lastname: Acilan
authors.forename: Eylem
authors.initials: E
authors.lastname: Tuncer
authors.forename: Seldag
authors.initials: S
authors.lastname: Bekpinar
authors.forename: Ahmet Tarik
authors.initials: AT
authors.lastname: Baykal
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005109:Extracellular Matrix; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007834:Lasers; D008297:Male; D042282:Microdissection / Q000379:methods*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D011506:Proteins
keywords: label-free proteomics; laser capture microdissection; protein expression; thoracic aortic aneurysm; vascular smooth muscle