Terapie farmacologiche nell'attivita degenerativa della metalloproteinasi-9 negli aneurismi dell'aorta addominale

Introduction. The development of abdominal aortic aneurysms (AAA) is associated with excessive proteolysis activity of the extracellular matrix (ECM), mediated by metal-proteinase (MMPs). Different drugs have shown modulatory effect on the production of MMP-9, mainly involved in the development of AAA, which can potentially influence the growth of the aneurysm itself. The aim of the study was to evaluate the influence of different pharmacological activities on the production of MMP in aortic aneurysmal tissues. Methods. Aneurysmal aortic wall segments were taken from AAA patients undergoing open surgical treatment. Mesenchymal stem cells (CSMs - associated with the production of MMP-9) derived from aortic wall were assayed for MMP-9 gene expression at baseline levels. Assessments of viability and gene expression of MMP-9 were than performed, using Real Time PCR in association with three different drugs: Pioglitazone, Sinvastatin and Doxycycline, at different concentrations. Results. The study was approved by the local ethics committee and 12 specimens of aortic wall from different patients were analysed. From all the segments, CSMs were obtained and tested using Real Time PCR. At the baseline sample without medication, an over-expression of MMP-9 was found, 400 times higher than in healthy controls (P = .0001). All the drugs tested were associated with the maintenance of the cellular vitality and showed a significant reduction in the expression of MM-9 (P <0.001) with values resulting from the analysis of Real Time by the comparative method of 2-ΔCt, of 0.46 for Pioglitazone (10 μM), 0.1 for Doxycycline (25 μM) and 0.58 for Sinvastatin (10 μM). Conclusions. The pharmacological activity tested was associated with a significant reduction of MMP-9 expression by the CSMs while maintaining the cell viability, this assessment let speculate a possible in vivo study of the different pharmacological activities in the slowing down of the AAA development.