Alessandro Della Corte1, Cesare Quarto1, Clotilde Castaldo2, Franca Di Meglio2, Daria Nurzynska2, Luca S. De Santo1, Marisa De Feo1, Michelangelo Scardone1, Stefania Montagnani2, Maurizio Cotrufo1; 1Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy; 2"Federico II" University - Department of Biomorphological and Functional Sciences, Naples, Italy
Objective: Apoptosis of medial smooth muscle cells (SMCs) is a feature of aortic dilatation with both bicuspid (BAV) and tricuspid aortic valves (TAV). The present study examined the possible relationships between cellular and extra-cellular changes in the media of dilated aortas with valve stenosis, also assessing the spatial patterns of expression of both extracellular matrix (ECM) remodeling and SMC changes at the level of the greater curvature (convexity, right antero-lateral aspect) and lesser curvature (concavity) of the ascending aorta.Methods: According to a previously introduced sampling protocol, aortic wall specimens were retrieved from the convexity and the concavity of 8 dilated and 10 aneurismal ascending aortas (aortic ratios <1.5 and >1.5 respectively) during surgery for aortic valve stenosis and from 3 heart donors for control. Morphometry, immunohistochemistry for matrix proteins involved in vascular remodelling, terminal transferase-mediated deoxy-uridine-triphosphate nick end labelling - TUNEL - for in situ detection of apoptotic cells were employed. Moreover, western-blot was performed for Bmf (Bcl2-modifying factor), a pro-apoptotic protein that inhibits pro-survival Bcl2 proteins in response to alterations of cell-matrix interaction (anoikis phenomenon).
Results: Collagens type I and III were more reduced at the convexity than at the concavity in dilated aortas (p<0.05), whereas fibronectin and tenascin expression was increased, especially in aneurysms. In BAV dilations the antero-lateral wall showed more pronounced ECM alterations and greater apoptotic indexes than in TAV dilations. In aneurysms (aortic ratio>1.5), greater numbers of SMCs/mm2 were found, especially in BAV convexity. The increase in apoptotic indexes in the aneurysm phase, compared to dilations, was not so evident in BAV convexity (p=0.22) as in both BAV concavity and TAV (p<0.05). A greater increment in Bmf-Bcl2 binding was found in BAV versus TAV.
Conclusion: A complex balance between survival/proliferative stimuli (fibronectin and tenascin increase) and apoptotic/degradative signals (Bmf) underlies the progressive phases of aortic enlargement. The differences in apoptosis and remodeling expression between greater and lesser curvature suggest that mechanical factors (i.e. expected wall stress overload at the convexity with aortic stenosis) may concur to affect this balance. SMC apoptosis could be initiated by Bmf, a factor involved in cell death due to loss of cell-matrix contacts as in anoikis.
Back to Annual Meeting
Back to Program Outline
