Polymorphisms of endothelial nitric oxide gene as strong risk factors of sporadic ascending aorta aneurysm

BACKGROUND: Endothelium-derived nitric oxide (NO) is produced by an oxidative reaction catalyzed by endothelial NO synthase (eNOS). A lot of study shows reduced levels of NO in patients with aneurysm and bicuspid aortic valve (BAV). We want to analyse the role of the influence of polymorphisms of eNOS in patients with sporadic thoracic ascending aneurysm no BAV related (S-TAA). METHODS: Aortic specimens were obtained from 64 patients (44 men and 20 women, age 63± 9.5 years) undergoing surgical repair of S-TAA. A control group of 68 subjects (34 men and 34 woman, age: 61.1 ± 5.8 years) was also enrolled. Histopathological and immunohistochemical analyses were performed. Furthermore, genotyping of two common and functional single nucleotide genetic polymorphisms (SNPs) of eNOS gene was executed. RESULTS: We identified three different phenotypes of S-TAA according to the severity of medial degeneration: low, moderate and elevated. No significant differences were detected in terms of clinical features. In contrast, significant difference were observed in term of apoptosis of smooth muscle cells and metalloproteinase concentrations. Genotyping analysis revealed a significant association between the - 786T/C eNOs SNP and the risk of S-TAA (OR=4.7(1.92-16.32), p=0.0002 by Fisher test). In addition, a significant association was detected between this SNP and elevated medial degeneration. The biological effect of this SNP is in determining low levels of eNOs and consequently a reduced NO amount, that contribute to elevated medial degeneration, plurifocal apoptosis and severe concentration of metalloproteinases. CONCLUSIONS: Thus, polymorphisms of eNOs gene seem to have a key role in the pathophysiology of S- TAA.