Influence of Statins in Artery Aneurysms

Aneurysm, Extracellular Matrix Alteration, Statin

The altered balance between the proteinases and their tissue inhibitors (TIMPS) is one of the pathogenetical mechanism of the aneurysmatic connective tissue degeneration. The increasement of protease, collagenase and elastase activity results indeed in a dramatic drop of collagen and elastin tissue and serum levels.Matrix Metalloproteinases (MMPs) are a group of proteolytic enzymes that along with their specific and non-specific inhibitors modulate the extracellular matrix composition. Recent studies have suggested an interesting role of microRNAs (miRNAs) in the regulation mechanisms of inflammation. The aim of our study is to analyse the influence of statin treatment on aneurysmatic disease by monitoring MMPs and miRNAs in aneurysmatic wall tissue and MMps blood levels.

The altered balance between the proteinases and their tissue inhibitors (TIMPS) is one of the pathogenetical mechanism of the aneurysmal connective tissue degeneration. The increase of protease, collagenase and elastase activity results indeed in a dramatic drop of collagen and elastin tissue and serum levels. Vessels wall strength decrease is associated with the blood flow shear stress and affects negatively the walls integrity, causing the aneurysmatic vessel degeneration. Matrix Metalloproteinases (MMPs) are a group of proteolytic enzymes that along with their specific and non-specific inhibitors modulate the extracellular matrix composition. So far, 25 MMPs have been discovered, in particular, the ones that will be considered in this study are: MMP-2, MMP-9, and neutrophil gelatinase-associated lipocalin (NGAL) a related protein which is able to control MMP-9 activities. Inflammation plays a central role in the pathogenetical pathway of aneurysmatic developement. Recent studies have suggested an interesting role of miRNAs in the regulation mechanisms of inflammation. miRNAs are short ribonucleic acid molecules usually composed of 20 to 25 nucleotides that can regulate mRNA transcription and protein translation by targeting the 3'-untranslated regions (3'-UTR) of target genes. miRNAs are involved in various physiological responses and pathological processes. Increasing evidence suggest that miRNAs are involved in inflammatory responses. In particular the ones that will be focused on this study are: miR-29b, miR-21, miR-181a, miR-150. Very often, patients with aneurysmatic disease are under statin treatment. Some Statins (Atorvastatin, Simvastatin or Rosuvastatin) with pleiotropic effects may also play a protective role by conditioning the progression of the aneurysmatic degeneration. The aim of our study is to analyse the influence of statin treatment on aneurysmatic disease by monitoring some MMPs and related molecules (MMP-2, MMP-9 and NGAL), miRNAs (the evaluation will be performed in aneurysmatic wall tissues and circulating blood levels). Patients affected by central and peripheral aneurysmatic disease will be recruited and then divided in two groups based on the dosage of the statin treatment: the first group with maximum statin daily dose (Atorvastatin 80 mg, Simvastatin 40 mg, Rosuvastatin 40 mg), the second group with minimum statin daily dose. The latter will be defined as the control group. Only patients which will fullfill the criteria to undergo surgical treatment will be recruited in the study in order to collect biological specimen of the aneurysmatic tissues . The investigation consist in: * taking a preoperative blood sample to evaluate the MMPs circulating levels * taking an aneurysmatic vessel wall histological sample with an intraoperative biopsy to evaluate the tissue MMPs and miRNAs levels. Previously, several studies suggested a role of MMPs (MMP-2 and MMP-9) and miRNAs in regulation of aneurysm developement, in particular miR29b, miR-181a, miR-21, miR-150. The comparison between MMPs Levels in the study group and in the control group might highlight a role for MMPs level as a marker of aneurysmatic disease progression, consequently allowing the patient's stratification by analysing the risk of aneurysmatic evolution and growth.

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