Abstract
Degenerative aortic stenosis (AS) is the most common worldwide cause of valve replacement. The aortic valve is a thin, complex, layered connective tissue with compartmentalized extracellular matrix (ECM) produced by specialized cell types, which directs blood flow in one direction through the heart. There is evidence suggesting remodeling of such ECM during aortic stenosis development. Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms. Aortic valve samples were collected from 18 patients which underwent aortic valve replacement (50% males, mean age of 74 years) and 18 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by 2D-LC MS/MS iTRAQ methodology. The results showed an altered expression of 13 ECM proteins of which 3 (biglycan, periostin, prolargin) were validated by Western blotting and/or SRM analyses. These findings are substantiated by our previous results demonstrating differential ECM protein expression. The present study has demonstrated a differential ECM protein pattern in individuals with AS, therefore supporting previous evidence of a dynamic ECM remodeling in human aortic valves during AS development.
Highlights
Analysis of the secretome of aortic valves which pointed out an outstanding role of valvular remodeling in the pathophysiological mechanisms of aortic stenosis (AS)
The data generated by liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis were searched against the human RefSeq database using Proteome Discoverer software (Thermo Scientific)
Valve dysfunction is characterized by a deregulation that depends upon the combined relationship between extracellular matrix (ECM), valve cells, and valve mechanics[3]
Summary
Analysis of the secretome of aortic valves which pointed out an outstanding role of valvular remodeling in the pathophysiological mechanisms of AS. Since many ECM proteins are involved in AS, and taking into account its high prevalence and the long course of this disease, a better understanding of AS at the molecular level may be possible through a proteomic approach. This powerful technique might provide useful information to better understand the development of the disease. It may offer a new gate for the discovery of novel potential biomarkers shed to blood by the aortic valve, which may allow detecting patients at risk of developing degenerative AS, as a starting point. Validation of 3 ECM proteins found altered was performed by orthogonal techniques (Western blotting and/or selected reaction monitoring (SRM))
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