RT Journal Article
T1 Modification of the Secretion Pattern of Proteases, Inflammatory Mediators, and Extracellular Matrix Proteins by Human Aortic Valve is Key in Severe Aortic Stenosis
A1 Álvarez Llamas, Gloria
A1 Martín Rojas, Tatiana
A1 Cuesta, Fernando De La
A1 Calvo, Enrique
A1 Gil Dones, Félix
A1 Dardé, Veronica
A1 López Almodovar, Luis
A1 Padial, Luis
A1 Lopez, Juan Antonio
A1 Vivanco Martínez, Fernando
A1 Barderas, Maria
AB One of the major challenges in cardiovascular medicine is to identify candidate biomarker proteins. Secretome analysis is particularly relevant in this search as it focuses on a subset of proteins released by a cell or tissue under certain conditions. The sample can be considered as a plasma subproteome and it provides a more direct approximation to the in vivo situation. Degenerative aortic stenosis is the most common worldwide cause of valve replacement. Using a proteomic analysis of the secretome from aortic stenosis valves we could identify candidate markers related to this pathology, which may facilitate early diagnosis and treatment. For this purpose, we have designed a method to validate the origin of secreted proteins, demonstrating their synthesis and release by the tissue and ruling out blood origin. The nLC-MS/MS analysis showed the labeling of 61 proteins, 82% of which incorporated the label in only one group. Western blot and selective reaction monitoring differential analysis, revealed a notable role of the extracellular matrix. Variation in particular proteins such as PEDF, cystatin and clusterin emphasizes the link between aortic stenosis and atherosclerosis. In particular, certain proteins variation in secretome levels correlates well, not only with label incorporation trend (only labeled in aortic stenosis group) but, more importantly, with alterations found in plasma from an independent cohort of samples, pointing to specific candidate markers to follow up in diagnosis, prognosis, and therapeutic intervention.
PB Elsevier
SN 1535-9484
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/94701
UL https://hdl.handle.net/20.500.14352/94701
LA eng
NO Álvarez Llamas, G., Martín Rojas, T., Cuesta, F. et al. «Modification of the Secretion Pattern of Proteases, Inflammatory Mediators, and Extracellular Matrix Proteins by Human Aortic Valve Is Key in Severe Aortic Stenosis». Molecular & Cellular Proteomics, vol. 12, n.o 9, septiembre de 2013, pp. 2426-39. DOI.org (Crossref), https://doi.org/10.1074/mcp.M113.027425.
NO This work was supported by grants from the Instituto de Salud Carlos III (FISPI070537, FISPI080970, FISPI080920, RD07/0064/0023, PI11/02239, PI11/01401, CP09/00229), Fondo de Investigación Sanitaria de Castilla la Mancha (FISCAM, PI2008/08; FISCAMPI2008/28) and Redes Temáticas de Investigación Cooperativa (FONDOS FEDER,RD06/0014/1015,RD12/0042/ 0071),CNIC.
NO Instituto de Salud Carlos III
NO European Commission
NO Junta de Comunidades de Castilla-La Mancha
DS Docta Complutense
RD 29 abr 2025