Characterisation of the Mechanisms Involved in Thoracic Aortic Aneurysm Formation in Bicuspid Aortic Valve Patients versus Tricuspid Aortic Valve: Clinical Implications of a Pilot Study

Objective: Different factors are involved in the onset of thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) versus patients with tricuspid aortic valve (TAV). However, the mechanisms driving TAA remain unclear. Thus, the identifying of the eventual different mechanisms involved in TAA development in patients with BAV versus TAV was performed Methods. Aorta specimens and DNA samples were collected from 24 BAV (18 men and 6 women; mean age: 54.2 ± 14.39 years) and 110 TAV (79 men and 31 women, mean age: 66± 9.8 years) patients. A control group of 128 subjects (61 men and 67 woman, mean age: 61.1±5.8 years) was also enrolled. Histopathological and immunohistochemical analyses were performed, as well as genotyping of ten polymorphisms. Results:In BAV ascending aortas, significant elevated plurifocal apoptosis of smooth muscle cells and MMP-9 amounts were detected. In contrast, TAV ascending aortas were characterized by significant severity of elastic fragmentation, cystic medial necrosis, medial fibrosis and inflammation. Furthermore, in BAV cases the -1562TMMP-9 and -735TMMP2 alleles represent independent risk factors for TAA. In TAV cases, the D ACE and +896ATLR4 alleles seem, while, to be the predictor factor for TAA risk. They, combined with hypertension and age, increase significantly both the microscopic lesions and inflammation. Conclusion: Thus, the involvement of different molecular, cellular and genetic mechanisms characterises the patho-hysiology of BAV and TAV. This might consent to identify potential molecular and genetic biomarkers to detect BAV subjects at high TAA risk, to monitor and treat differently to those with TAV.