Role of Matrix Metalloproteinases in complications of thoracic aortic aneurysm

Abstract

Objectve: Metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix remodelling, associated with both physiopatological processes of several human tissues and systems, such as vascular system. It is well known their involvement in mediating both beneficial and pathological aorta effects, such as abdominal orta aneurysms and its complcations. On the contrary, unclear data exist about their role in the pathophysiology of sporadic thoracic aneurysm (TAA) and its complications. Thus, the aim of this study was to nalyse the role of MMPs in TAA complications, i.e. rupture and dissection.Methods: Aortic specimens obtained from 73 patients (51 men and 22 women, age 61.7 years) affected by TAAs, 18 patients with type A aortic dissection (TAD) and 30 controls were utilised for histopathological and immne-histochemical analyses. In addition, a second group of 128 subjects (61men and 67 womem, age 61.7 years) was enrolled to examine the role of single nucleotide polymorphirms (SNPs) of MMP-9 and MMP-2 genes in disease risk. Results: Three different patterns of MMPs(extracellular, intracellular, and mixed) with different concentration (low, moderate, elevated) have been observed in case aorta samples. The pattern with elevated MMP amount in aorta samples from TAD cases was also characterised by increased cystic medial degeneration, whitout substitutive fibrosis, and plurifocal apoptosis. In the context of TAA aorta samples, we identified three phenotypes. In particular, the phenotype III mainly observed in case samples showed the same histological features of TAD with elevated MMP concentration with a mixed pattern. in addition, significant associations were obserbved between the -1562C/T MMP9, -735C/T MMP2 SNPs and the risk of both TAA and TAD. Conclusions: OUR data suggest a crucial role of both MMP-2 and -9 in both TAA and its complications. such as TAD. in future they might be considered as new criteria in TAA surgical indications.