Abstract 3545: Differential Extracellular Matrix Gene Expression in Human Aortic Diseases
Objective Extracellular matrix (ECM) degradation is closely regulated by matrixmetalloprotein-ases (MMPs) and their tissue inhibitors (TIMPs). Aim of this study was to evaluate differences in the patterns of MMP and TIMP expression in relation to different diseases of the thoracic aorta.
Methods Human aortic tissue from aneurysms (AA, n=13, 60yrs), dissection (AD, n=2, 57yrs), coarctation (AC, n=8, 11d), post stenotic aortic dilatation (AS, n=11, 73yrs) and patients having aortic valve incompetence (AVI, n=2, 39yrs) together with control tissue (n=19, 68yrs) obtained during routine coronary artery bypass grafting was evaluated using immunohistochemistry and competitive PCR. Pair wise fixed reallocation randomization test statistics were then performed.
Results In AA MMP-9 and TIMP-2, -3, -4 expression levels were decreased (p<0.05). No significant differences in expression levels were detected for the remaining MMPs and TIMPs. In AS and AD no significant changes in MMP or TIMP expression levels was observed. In AI TIMP-1 expression was significantly elevated. No statistical significance was reached for any MMP. In CA a downregulation for MMP-9 and TIMP-3 was measured. Other changes in mRNA-expression for the remaining MMPs and TIMPs did not reach statistical significance.
Conclusions MMPs and TIMPs are synthesized in diseased aortic tissue suggesting their involvement in matrix remodelling. Similarities among aneurysms (AA) and aortoocclusive diseases (AOD) were observed. While MMP-9 and TIMP-3 downregulation can be found in AA and AOD altered expression of several genes might play a role in disease differentiation. Key words: aneurysm, stenosis, aorta, tissue inhibitors, metalloproteinases, polymerase chain reaction, immunohistochemistry