Background. The Ross operation uses a viable, pulmonary autograft valve to replace the aortic, making it an attractive therapy in growing children and young adults. Pulmonary autograft root dilatation, which appears in as many as 20-30% of late survivors, represents the major long-term complication and leading cause of re-operation. To define whether adaptive remodeling of the pulmonary artery root may occur, when chronically exposed to systemic circulation, a proteomic study of aneurismal pulmonary autografts was undertaken. Methods. At our center 7 patients, aged 36±16 years (range 15-51), who presented with pulmonary autograft root aneurysm, at an average of 12±3 years (range 8-15) after Ross procedure, underwent re-operation. Patients were matched for age and gender with 9 control subjects (cardiac donors) from whom a specimen of main pulmonary artery were collected. From each patient biopsy of non-coronary sinus of Valsalva were taken. The proteomic studies were performed on tunicae mediae protein lysates of either group, prefractionated into five sets (pH 3.0−4.6, 4.5−5.5, 5.3−6.3, 6.2−7.0, 7.0−10.0). These fractions were analyzed by means of bidimensional electrophoresis (2-DE) coupled with MALDI-TOF/MS and PMF analysis, and validated by Western-blotting. Results. Preliminary evidence from proteomic analyses in patients who develop root aneurysm late after the Ross procedure shows differences in the protein pattern in comparison to the controls. Significant increases occured in the expression of proteins related to focal adhesions (i.e. Paxillin), cytoskeleton (i.e Vimentin), and to cell proliferation (i.e. Jagged1). Conversely, cystathionine g-lyase (CTH), an enzyme producing H2S, was remarkably downregulated. Conclusion. This is the first elucidation of some of the pathophysiological mechanisms underlying the autograft root aneurysm. Moreover, they support the view that a proper adaptive remodeling of the pulmonary autograft root when exposed to the systemic circulation does not occur.
Pulmonary artery root aneurysm after the Ross procedure: a proteome study
MARCONI, Maddalena;CHIARINI, Anna Maria;DAL PRÀ, Ilaria Pierpaola;ARMATO, Ubaldo;FAGGIAN, Giuseppe;LUCIANI, GIOVANNI BATTISTA
2011-01-01
Abstract
Background. The Ross operation uses a viable, pulmonary autograft valve to replace the aortic, making it an attractive therapy in growing children and young adults. Pulmonary autograft root dilatation, which appears in as many as 20-30% of late survivors, represents the major long-term complication and leading cause of re-operation. To define whether adaptive remodeling of the pulmonary artery root may occur, when chronically exposed to systemic circulation, a proteomic study of aneurismal pulmonary autografts was undertaken. Methods. At our center 7 patients, aged 36±16 years (range 15-51), who presented with pulmonary autograft root aneurysm, at an average of 12±3 years (range 8-15) after Ross procedure, underwent re-operation. Patients were matched for age and gender with 9 control subjects (cardiac donors) from whom a specimen of main pulmonary artery were collected. From each patient biopsy of non-coronary sinus of Valsalva were taken. The proteomic studies were performed on tunicae mediae protein lysates of either group, prefractionated into five sets (pH 3.0−4.6, 4.5−5.5, 5.3−6.3, 6.2−7.0, 7.0−10.0). These fractions were analyzed by means of bidimensional electrophoresis (2-DE) coupled with MALDI-TOF/MS and PMF analysis, and validated by Western-blotting. Results. Preliminary evidence from proteomic analyses in patients who develop root aneurysm late after the Ross procedure shows differences in the protein pattern in comparison to the controls. Significant increases occured in the expression of proteins related to focal adhesions (i.e. Paxillin), cytoskeleton (i.e Vimentin), and to cell proliferation (i.e. Jagged1). Conversely, cystathionine g-lyase (CTH), an enzyme producing H2S, was remarkably downregulated. Conclusion. This is the first elucidation of some of the pathophysiological mechanisms underlying the autograft root aneurysm. Moreover, they support the view that a proper adaptive remodeling of the pulmonary autograft root when exposed to the systemic circulation does not occur.
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