Purpose-Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, frequently associated with significant ascending aortic aneurysms. The pathogenesis of medial degeneration of the aorta in BAV disease remains not defined. A proteomic characterization of proteins which are actively synthesized and secreted (secretome) may represent a useful strategy in order to identify molecular pathways and novel biomarkers. We compared the secretomes of ascending aortic aneurysms collected from patients affected by BAV and patients with tricuspid aortic valve (TAV). Methods-Each samples of the ascending aortic aneurysm was incubated for 24 h in serum-free RPMI. Released proteins were digested with trypsin. Peptide mixtures were fractioned by nano-HPLC and analyzed by MALDI mass spectrometry. Proteins reported as differentially modulated resulted statistical validated across 6 replicates (T-test >95%; pvalue <0.05). Results-With our proteomics investigation we were able to identify 112 released proteins and/or degradation products of cellular proteins. Of these, 11 proteins resulted differentially modulated between BAV and TAV samples (two examples are reported in the Figure). Interestingly, the majority of these factors are extracellular matrix components and result to be over-expressed in BAV disease suggesting an important and increased activity of degrading processes (matrix-metalloproteinases) on extracellular components. Conclusions: A proteomic approach enabled us to identify factors released by aneurismal tissues as well as to observe differences between BAV and TAV specimens. Our experimental strategy intends to disclose molecular components involved in disease onset and development, released by tissues into body fluids and thus easily measurable in blood for diagnosis and prognosis.
Differences in the secretome of ascending aortic aneurysms from patients with bicuspid or tricuspid valves
CECCHETTINI, ANTONELLA
2011-01-01
Abstract
Purpose-Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, frequently associated with significant ascending aortic aneurysms. The pathogenesis of medial degeneration of the aorta in BAV disease remains not defined. A proteomic characterization of proteins which are actively synthesized and secreted (secretome) may represent a useful strategy in order to identify molecular pathways and novel biomarkers. We compared the secretomes of ascending aortic aneurysms collected from patients affected by BAV and patients with tricuspid aortic valve (TAV). Methods-Each samples of the ascending aortic aneurysm was incubated for 24 h in serum-free RPMI. Released proteins were digested with trypsin. Peptide mixtures were fractioned by nano-HPLC and analyzed by MALDI mass spectrometry. Proteins reported as differentially modulated resulted statistical validated across 6 replicates (T-test >95%; pvalue <0.05). Results-With our proteomics investigation we were able to identify 112 released proteins and/or degradation products of cellular proteins. Of these, 11 proteins resulted differentially modulated between BAV and TAV samples (two examples are reported in the Figure). Interestingly, the majority of these factors are extracellular matrix components and result to be over-expressed in BAV disease suggesting an important and increased activity of degrading processes (matrix-metalloproteinases) on extracellular components. Conclusions: A proteomic approach enabled us to identify factors released by aneurismal tissues as well as to observe differences between BAV and TAV specimens. Our experimental strategy intends to disclose molecular components involved in disease onset and development, released by tissues into body fluids and thus easily measurable in blood for diagnosis and prognosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
