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Identifier 000371469
Title Μελέτη της έκφρασης των μεταλλοπρωτεασών και των αναστολέων τους στα ανευρίσματα της ανιούσης αορτής
Alternative Title Study of the expression of matrix metalloproteases and their inhibitors in ascending aorta aneurysms
Author Τσαρούχας, Κωνσταντίνος
Thesis advisor Σπαντίδος, Δ
Abstract The events that result in the establishment and progression of aortic aneurysms are complex and multifactorial. However, degradation of the extracellular matrix (ECM) of aortic tunica media appears to be a consistent histopathological and biochemical feature. An increased local expression of matrix metalloproteinases (MMPs) as well as an imbalance between MMP expression and the expression of their natural tissue inhibitors (TIMPs) have been demonstrated in dilated aortic wall. We hypothesized that a distinct MMP and TIMP expression pattern underlies the development of ascending aorta dilation. To test our hypothesis, transcriptional expression levels of 10 MMPs and 4 TIMPs were assessed by real-time PCR in dilated and normal aortic tissue derived from patients that underwent elective surgical repair of ascending aorta aneurysm (AAA) and coronary artery by-pass grafting, respectively. We found no statistically significant up- or down-regulation of any individual MMP. Surprisingly, the tissue inhibitor of metalloproteinases (TIMP)-3 was significantly more expressed in dilated aortic tissue compared to control tissue, thereby reflecting an effort to counteract MMP activity. Finally, when we evaluated the MMP and TIMP co-expression pattern in normal and dilated aortic tissue, we observed that in aortic aneurysms activation of the MMP system was characterised by the coexpression of more than one proteinase and the down-regulation of TIMP-1 and -2. The latter observation is the key regulatory point that leads to ECM degradation and, subsequently, to AAA formation. Data from recent publications suggest an association between abdominal aneurysms and elevated plasma homocysteine (Hcy). No published evidence correlates AAA size, Hcy and MMPs activity. In the framework of the present thesis, we also 15 attempted to identify whether serum Hcy in 27 patients operated for AAA is associated with aneurysm diameter, circulating and tissue protein levels of MMP-3 and MMP-9 and their mRNA tissue expression. Only 43% of the patients of our study group had abnormal Hcy levels (15.0μmol/L΄&λτHcy΄&λτ35.9μmol/L). Circulating MMP-3 (6.44±4.20ng/mL) and MMP-9 (134±11.4ng/mL) were elevated compared to reference values (p΄&λτ0.001). Tissue MMP-3 and MMP-9 concentrations and circulating MMP-9 positively correlated with Hcy (r=0.461,p=0.014; r=0.526, p=0.024; r=0.773, p=0.011, respectively). Aneurysm diameter didn’t statistically correlate with either Hcy or MMP-3 and MMP-9 protein levels in both serum and tissue, although all three markers were elevated in aneurysm diameters ΄&γτ55mm. Our results suggest that Hcy, even in patients with mild hyperhomocysteinaemia, could be involved in the pathophysiology of AAA, through regulation of MMP-3 and MMP-9 activity.
Language Greek
Subject Ascending aorta aneurysms
Cardiovascular system
Homocystene
Matrix metalloproteases
mRNA
Μεταγραφική έκφραση
Μεταλλοπρωτεάσες
Ομοκυστείνη
ανεύρυσμα ανιούσης αορτής
Issue date 2011-04-12
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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