Differential expression of MMP-2, MMP-9 and TIMP proteins in thoracic aortic aneurysm – comparison with and without bicuspid aortic valve: a meta-analysis

摘要

Background: It is believed that the balance of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), in the aorta, play a critical role in aneurysm formation. The objective of this study was to perform a meta-analysis of studies reporting protein expression of MMPs and TIMPs in the ascending aorta of thoracic aortic aneurysms (TAA) cases and to examine this expression in persons with TAA and bicuspid aortic valves (BAV). Methods: OvidSP Medline and EMbase were systematically searched for studies that were: human ascending TAA cases with measurement of MMP or TIMP protein expression in the aorta and a control group. A similar search was conducted for BAV compared to those with a normal or trileaflet aortic valve (TAV). Results: Eight studies fulfilled the inclusion criteria. There was a significant increase in MMP-9 and no change in MMP-2, in the aorta from persons with TAA (N = 106) compared to control (N = 30). There was also a highly significant reduction in TIMP-1 and TIMP-2 in TAA (N = 93) compared to control (N = 24) resulting in a MMP-9 to TIMP-1 or TIMP-2 ratio over 3.5 fold greater than controls. There was a highly significant increase in MMP-2 but not MMP-9 in TAA with BAV (N = 112) compared to TAV (N = 53). There was a significant reduction for TIMP-1 in BAV compared to TAV but no change in TIMP-2, TIMP-3 or TIMP-4. Conclusions: These data suggest that MMP may be implicated in the pathogenesis of TAA and there is a differential expression with MMP-9 increased and TIMP-1 and -2 reduced in the most common forms of TAA. MMP-2 is increased and only TIMP-1 decreased in TAA with BAV compared to TAV.