Structural and biomolecular changes in aorta and pulmonary trunk of patients with aortic aneurysm and valve disease: implications for the Ross procedure.

OBJECTIVES

A higher incidence of pulmonary autograft dilatation is assumed in patients with ascending aortic dilatation and bicuspid aortic valve disease. To examine whether structural abnormalities are present in the ascending aorta as well as in the pulmonary trunk (PT) we specifically addressed molecular mechanisms and signalling pathways for aneurysm formation in ascending aortic aneurysms and PT of patients with different aortic valve pathology undergoing an extended Ross procedure.

METHODS

Wall segments resected from aortic aneurysms (20 patients, 7 bicuspid aortic valves BAV, and 13 tricuspid aortic valves TAV) and from PTs were submitted to analysis of leukocyte infiltration (immunohistochemistry), smooth muscle cell (SMC) apoptosis (in situ end-labelling of DNA-fragments TUNEL), and expression of death-promoting proteins perforin, granzyme B, Fas/FasL (immunoblotting).

RESULTS

Degenerative changes including rarefication and apoptosis of SMCs were significantly more severe in BAV than TAV disease (apoptotic index 9.2+/-3.2 vs. 11.9+/-6.2, P = 0.02). Immunohistochemistry confirmed presence and activation of death-promoting mediators in aneurysmal tissue whereas pulmonary tissue displayed only few apoptotic cells, occasional Fas+cells, rarely colocalized with FasL. By Western blot analysis extracts from BAV and TAV but not pulmonary artery wall contained appreciable amounts of perforin, granzyme B, and Fas/FasL.

CONCLUSION

Aneurysm formation is associated with SMC apoptosis and local signal expression of activated cells in patients with bicuspid as well as TAV. The PT itself is not pathologically involved with only minor degenerative changes. Although the disease process in the aorta appeared to be more severe in patients with BAV, there was similarity of histological and molecular changes of the pulmonary artery wall in all patients. Dilation of the pulmonary autograft seems not to be the result of histopathological and biomolecular mechanisms in the PT.