Spatial Patterns of Matrix Protein Expression in Dilated Ascending Aorta with Aortic Regurgitation: Congenital Bicuspid Valve versus Marfan’s Syndrome

Alessandro Della Corte, Luca S. De Santo, Stefania Montagnani, Cesare Quarto, Gianpaolo Romano, Cristiano Amarelli, Michelangelo Scardone, Marisa De Feo, Maurizio Cotrufo, Giuseppe Caianiello
Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, V. Monaldi Hospital, Naples, Department of Biomorphological and Functional Sciences, Federico II University, Secondo Policlinico, Naples, Italy

 

Background and aim of the study: Aortic wall stress has been shown to increase locally at the convex aspect of the ascending tract when axial root motion is increased, as occurs in aortic valve regurgitation. The study aim was to assess the expression of extracellular matrix (ECM) proteins involved in stress-induced vascular remodeling in the convexity and the concavity of dilated ascending aortas with aortic valve regurgitation.
Methods: Aortic wall specimens, harvested at the convexity and concavity of eight dilated ascending aortas with severe aortic valve regurgitation underwent morphometry, Western blot, RT-PCR and confocal immunohistochemistry. Five patients (group A) had congenital bicuspid aortic valve (BAV), and three (group B) had Marfan’s syndrome. Specimens from the aorta of three multi-organ donors served as controls.
Results: At morphometry, medial degeneration was more severe in the convexity than in the concavity, especially in group A. Western blot, RT-PCR and immunohistochemistry disclosed an asymmetric

pattern in the expression of some ECM proteins (laminin, tenascin, fibronectin). Fibronectin was increased in the convexity of both groups compared to controls at Western blot. Immunohistochemistry confirmed this pattern only in BAV. Higher levels of tenascin were found in the convexity in group A. The laminin content was greater in the concavity than in the convexity of both groups, but in group B the type of laminin was different, with the b2 chain particularly expressed, and almost absent in non-Marfan patients. Type I and type III collagens were more markedly reduced in the convexity than in the concavity in BAV. In group B, type I collagen was decreased and type III increased, but without any significant difference between the two aspects of the aorta.
Conclusion: A tissue remodeling response to valve disease-related wall stress may underlie aortic dilatation with BAV regurgitation. Although morphometry showed similar changes in Marfan aortas, molecular investigations differentiated this condition, qualitatively, from BAV.
The Journal of Heart Valve Disease 2006;15:20-27
 
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