Pathophysiological implications of Inflammation and Genetic Inflammatory Factors in hypertensive and old patients affected by thoracic Aortic Aneurysm

Background: Sporadic thoracic aortic aneurysm (S-TAA) is potentially devastating with severe morbidity and mortality. Current evidence suggests inflammation as main mechanism of its pathophysiology associated with both ageing and age-related hypertension. Thus, we assessed whether inflammation is the principal mechanism of medial degeneration in hypertensive and old S-TAA individuals. Methods: Histo-pathological and immunoistochemical aorta examination was executed. Furthermore, genotyping of ten SNPs 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 and -1562 C/T MMP-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. Conclusions: Results obtained agree emerging evidence of inflammation as shared pathological mechanism for S-TAA, suggesting the role of inflammatory products and genetic profile as possible S-TAA risk biomarkers.