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iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease.

Martin-Rojas T, Mourino-Alvarez L, Alonso-Orgaz S, Rosello-Lleti E, Calvo E, Lopez-Almodovar LF, Rivera M, Padial LR, Lopez JA, de la Cuesta F, Barderas MG - Sci Rep (2015)

Bottom Line: Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

(A) Biological implications of the 56 differentially expressed proteins according to the functional annotation clustering. (B,C) Protein-protein interaction networks were studied using the STRING v9.1 web-tool. Analyses of the 56 dysregulated proteins (B) and ECM proteins (C) are shown. Proteins with the same circle colours correspond to the same cluster, according to the classification performed using this tool.
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f3: (A) Biological implications of the 56 differentially expressed proteins according to the functional annotation clustering. (B,C) Protein-protein interaction networks were studied using the STRING v9.1 web-tool. Analyses of the 56 dysregulated proteins (B) and ECM proteins (C) are shown. Proteins with the same circle colours correspond to the same cluster, according to the classification performed using this tool.

Mentions: Functional analysis of the altered proteins was performed using DAVID v6.7. Molecular functions and biological processes were explored through the functional annotation tool to generate clusters of overrepresented Gene Ontology (GO) terms. This analysis showed 13 significant clusters where the most significant cluster was formed by proteins from the extracellular region or matrix. This cluster is composed of 24 proteins of which 13 correspond to ECM proteins. Among most significantly enriched terms we observed oxidative stress, inflammatory response and proteins related to muscle and cytoskeleton. ECM proteins together with oxidative stress proteins are primarily involved in the biological AS process (Fig. 3A).


iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease.

Martin-Rojas T, Mourino-Alvarez L, Alonso-Orgaz S, Rosello-Lleti E, Calvo E, Lopez-Almodovar LF, Rivera M, Padial LR, Lopez JA, de la Cuesta F, Barderas MG - Sci Rep (2015)

(A) Biological implications of the 56 differentially expressed proteins according to the functional annotation clustering. (B,C) Protein-protein interaction networks were studied using the STRING v9.1 web-tool. Analyses of the 56 dysregulated proteins (B) and ECM proteins (C) are shown. Proteins with the same circle colours correspond to the same cluster, according to the classification performed using this tool.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664895&req=5

f3: (A) Biological implications of the 56 differentially expressed proteins according to the functional annotation clustering. (B,C) Protein-protein interaction networks were studied using the STRING v9.1 web-tool. Analyses of the 56 dysregulated proteins (B) and ECM proteins (C) are shown. Proteins with the same circle colours correspond to the same cluster, according to the classification performed using this tool.
Mentions: Functional analysis of the altered proteins was performed using DAVID v6.7. Molecular functions and biological processes were explored through the functional annotation tool to generate clusters of overrepresented Gene Ontology (GO) terms. This analysis showed 13 significant clusters where the most significant cluster was formed by proteins from the extracellular region or matrix. This cluster is composed of 24 proteins of which 13 correspond to ECM proteins. Among most significantly enriched terms we observed oxidative stress, inflammatory response and proteins related to muscle and cytoskeleton. ECM proteins together with oxidative stress proteins are primarily involved in the biological AS process (Fig. 3A).

Bottom Line: Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.

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.

No MeSH data available.


Related in: MedlinePlus