TY - JOUR
T1 - Locally different proteome in aortas from patients with stenotic tricuspid and bicuspid aortic valves†
AU - Forte, Amalia
AU - Yin, Xiaoke
AU - Fava, Marika
AU - Bancone, Ciro
AU - Cipollaro, Marilena
AU - De Feo, Marisa
AU - Mayr, Manuel
AU - Jahangiri, Marjan
AU - Della Corte, Alessandro
PY - 2019/9/1
Y1 - 2019/9/1
N2 - OBJECTIVES: We aimed to compare the intracellular proteome of ascending aortas from patients with stenotic bicuspid (BAV) and tricuspid aortic valves (TAV) to identify BAV-specific pathogenetic mechanisms of aortopathy and to verify the previously reported asymmetric expression of BAV aortopathy [concentrated at the convexity (CVX)] in its 'ascending phenotype' form. METHODS: Samples were collected from the CVX and concavity sides of non-aneurysmal ascending aortas in 26 TAV and 26 BAV patients undergoing stenotic aortic valve replacement. Aortic lysates were subjected to cellular protein enrichment by subfractionation, and to proteome comparison by 2-dimensional fluorescence difference in-gel electrophoresis. Differentially regulated protein spots were identified by liquid chromatography-tandem mass spectrometry and analysed in silico. Selected results were verified by immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: In BAV samples, 52 protein spots were differentially regulated versus TAV samples at the CVX and 10 spots at the concavity: liquid chromatography-tandem mass spectrometry identified 35 and 10 differentially regulated proteins, respectively. Charge trains of individual proteins (e.g. annexins) suggested the presence of post-translational modifications possibly modulating their activity. At the CVX, 37 of the 52 different protein spots showed decreased expression in BAV versus TAV. The affected biological pathways included those involved in smooth muscle cell contractile phenotype, metabolism and cell stress. CONCLUSIONS: The observed differential proteomics profiles may have a significant impact on the pathogenesis of the aortopathy, pointing the way for further studies. At a preaneurysmal stage, an aorta with BAV shows more protein expression changes and potentially more post-translational modifications at the CVX of the ascending aorta than at the concavity, compared to that of TAV.
AB - OBJECTIVES: We aimed to compare the intracellular proteome of ascending aortas from patients with stenotic bicuspid (BAV) and tricuspid aortic valves (TAV) to identify BAV-specific pathogenetic mechanisms of aortopathy and to verify the previously reported asymmetric expression of BAV aortopathy [concentrated at the convexity (CVX)] in its 'ascending phenotype' form. METHODS: Samples were collected from the CVX and concavity sides of non-aneurysmal ascending aortas in 26 TAV and 26 BAV patients undergoing stenotic aortic valve replacement. Aortic lysates were subjected to cellular protein enrichment by subfractionation, and to proteome comparison by 2-dimensional fluorescence difference in-gel electrophoresis. Differentially regulated protein spots were identified by liquid chromatography-tandem mass spectrometry and analysed in silico. Selected results were verified by immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: In BAV samples, 52 protein spots were differentially regulated versus TAV samples at the CVX and 10 spots at the concavity: liquid chromatography-tandem mass spectrometry identified 35 and 10 differentially regulated proteins, respectively. Charge trains of individual proteins (e.g. annexins) suggested the presence of post-translational modifications possibly modulating their activity. At the CVX, 37 of the 52 different protein spots showed decreased expression in BAV versus TAV. The affected biological pathways included those involved in smooth muscle cell contractile phenotype, metabolism and cell stress. CONCLUSIONS: The observed differential proteomics profiles may have a significant impact on the pathogenesis of the aortopathy, pointing the way for further studies. At a preaneurysmal stage, an aorta with BAV shows more protein expression changes and potentially more post-translational modifications at the CVX of the ascending aorta than at the concavity, compared to that of TAV.
KW - 2-dimensional fluorescence difference in-gel electrophoresis
KW - Aortopathy
KW - Bicuspid aortic valve
KW - Liquid chromatography–tandem mass spectrometry
KW - Proteome subfractionation
UR - http://www.scopus.com/inward/record.url?scp=85062415527&partnerID=8YFLogxK
U2 - 10.1093/ejcts/ezz032
DO - 10.1093/ejcts/ezz032
M3 - Article
C2 - 30805593
AN - SCOPUS:85062415527
SN - 1873-734X
VL - 56
SP - 458
EP - 469
JO - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
JF - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
IS - 3
ER -