Ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve: involvement and clinical relevance of smooth muscle cell apoptosis and expression of cell death-initiating proteins.
OBJECTIVE
There is relationship between a dilated ascending aorta and a bicuspid aortic valve. Controversy exists concerning techniques available for surgical restoration of the functional and anatomical integrity of the aortic root. The present study was undertaken to define the histopathologic and molecular biologic condition of ascending aortic aneurysms associated with bicuspid (BAV) or tricuspid aortic valve (TAV) and the relationship to valve sparing or pulmonary autograft procedures.


METHODS
Aortic aneurysm wall specimens from 20 patients (10 BAV; 10 TAV) undergoing elective repair and normal aortic tissues from organ donors (n=5) were analysed for patterns of smooth muscle cells (SMCs) and infiltrating leukocytes (immunohistochemistry), apoptosis (in situ end-labelling of DNA-fragments (TUNEL)), and expression of the death-promoting proteins perforin, Fas, and FasLigand (Immunoblotting).


RESULTS
Segments from aneurysms exhibited a distinct pattern of medial destruction, elastic fragmentation, and disorientation with rarefication of SMCs. BAV wall segments contained more cells bearing markers of apoptosis than TAV specimens whereas normal aorta displayed only few apoptotic cells (P<0.05). TUNEL showed higher levels of DNA fragmentation in BAV than in TAV, and double immunostaining identified SMCs as the principal cell type displaying fragmented DNA. Immunohistochemistry confirmed expression of death-promoting mediators by infiltrating lymphocytes, and Western blotting documented their presence in BAV and TAV aneurysmal tissue, with the greatest increases seen in specimens from aneurysms associated with BAV.


CONCLUSIONS
There is evidence for a molecular link between SMC apoptosis initiated by infiltration and local signal expression of immune cells and weakening of the aortic wall being more prevalent in patients with BAV. Our findings may suggest a mechanism responsible for aneurysm formation of the aorta and aortic dilatation after autograft root or sinus remodelling procedures.
Schmid
Franz-Xaver
FX
Department of Cardiothoracic and Vascular Surgery, University of Regensburg, Regensburg, Germany. franz-xaver.schnid@klinik.uni-regensburg.de
Bielenberg
Katrin
K
Schneider
Anette
A
Haussler
Andreas
A
Keyser
Andreas
A
Birnbaum
Dietrich
D
D000368:Aged; D001011:Aorta / Q000737:chemistry; D001014:Aortic Aneurysm / Q000150:complications* / Q000276:immunology / Q000473:pathology; D001021:Aortic Valve / Q000002:abnormalities* / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor / Q000032:analysis
D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin