CRT-723 Is the Sporadic Thoracic Aortic Aneurysm the Result of an Inflammatory Process?

Background: Sporadic thoracic aortic aneurysm (S-TAA) is potentially devastating with severe morbidity and mortality. The histopathologic underlying abnormality of both ascending aortic aneurysm and dissection is medial degeneration, a pathological entity initially described as no inflammatory lesions of smooth muscle cells and elastic fibres. Accordingly, this study sought to determine whether inflammation characterize medial degeneration and the onset and progression of S-TAA. Methods: Aortic specimens were obtained from patients (31 men and 11 women, whose median age 66.16 ` 5.87 years) undergoing surgical repair of TAA (n1⁄424) and TAD (n1⁄418). Histo-pathological and immunoistochemical aorta examinations were executed. Furthermore, genotyping of ten SNPs (single nucleotide polymorphisms) in cases and controls was performed. Plasma inflammatory molecules were also detected in patients and controls using ELISA technique. Results: A significant inflammatory/immune CD3+CD4+CD8+CD68+CD20+ cellular infiltrate mainly in vasa vasorum of adventitia was observed in case aortas, suggesting its possible migration from these vessels into media and its role in destroying of all components of extracellular matrix and vascular smooth muscle cells (VSCM)s. Consistent of these data, significant higher plasma levels of systemic inflammatory mediators characterized the cases. Different aorta abnormalities, apoptosis of VSCMs and severe MMP-9 amounts were also found in S-TAA aortas. In addition, five very significant associations with S-TAA risk were detected. Of these, D/I ACE (Angiotensin Converting Enzyme) and -1562 C/T MMP-9 (Metalloproteinases-9) SNPs are independent risk factors for S-TAA. Higher tissue and plasma levels of MMP-9 were also observed in -1562T MMP-9 allele carriers. A high S-TAA risk genotype was also detected significantly associated with high levels of systemic inflammatory mediators, immune/inflammatory cells and hypertension. Conclusion: Results obtained are encouraging and lead to suppose that inflammation also is a shared pathological mechanism for S-TAA. On the other hand, they are in agreement with the emerging evidence suggesting the role of inflammation in several aorta diseases, such as S-TAA