| IntroductionMatrix metalloproteinases (MMPs) , a family of endopeptidases involved in degradation of extracellular matrix proteins, are of central relevance in the patho-genesis of an abdominal aortic aneurysm( AAA). In particular, MMP -2( gelati-nase A) has been shown to be important in the destructive process accompanying aneurysm development. Most MMPs, including MMP - 2, are produced and generally secreted in a latent form that requires stepwise activation through interactions with a variety of proteins, including membrane type (MT) —MMPs. An increase of MT1 - MMP expression in AAA patients has been observed when compared with nonaneurysmal aorta.The objective of this study was to identify the expression and activity of MT1 - MMP and MMP - 2 in an experimental rodent elastase - induced AAA model.Materials and Methods1, Thirty Wistar rats were randomly divided into 2 groups;experimental group and control group (n = 15). Aortas were perfused with elastase or saline as a control。 The diameter of abdominal aorta was measured before and after perfusion. Wistar rats were randomly divided into 2d,4d,7d groups(n =5).2,The abdominal aorta was harvested on the postoperative days 2,4,7 respectively. AAA was defined as increase in diameter by at least 100% over preperfusion diameter.3NImmunohistochemical staining was used to detect the expression of MMP -2 and MTl-MMP.4NThe mRNA expression of MMP -2 and MTl - MMP were measured by RT-PCR.5NStatistic analysis:Data were processed by t -test and x2 -test.Results1 ^Aneurysms formed in 80% of the elastase - perfused aortas at 7 days, whereas none formed in the saline — perfused aortas.2 >, Immunohistochemical staining: MTl - MMP was detectable only in the elastase - perfused aortas at day 7, whereas MMP - 2 was increased in elastase— perfused aortas compared with saline — perfused aortas. ( p < 0.05)3NRT -PCR: Significantly increased MTl -MMP expression was observed only on day 4, when levels were 2. 2 — fold higher in elastase — perfused aortas compared with saline — perfused aortas(p <0. 01) , whereas MMP -2 expression was similar between the saline - perfused aortas and elastase perfused aortas.DiscussionExperimental abdominal aortic aneurysm model induced by perfusing elastase was founded by Anidjar. In this procession MMPs are increased. MMPs including MMP - 2 are produced and secreted in latent form that requires activation. MTl - MMP may be important in MMP - 2 activation. *A human study has implicated MTl - MMP activity in AAA was based on its activity of cleaving the latent 72 - kD MMP - 2 to its activated 62 - kD form. Study also demonstrated a significant proportion of proMMP - 2 in the normal aorta and a greater proportion of activated MMP - 2 in diseased aorta. Furthermore , in vitro studies in which MTl - MMP was depleted resulted in insignificant amounts of MMP - 2 activation compared with normal, emphasizing the role of MTl - MMP in the activation of MMP -2.In this study MTl — MMP expression significantly increased at day 4 inelastase - perfused aortas as compared saline - perfused aortas. By day 7 , MTl - MMP expression in elastase - perfused aortas had decreased to expression levels similar to the saline - perfused aortas, suggesting that transiently expressed during aneurysm formation. Increased MMP - 2 activity also become significant on day 7 , suggesting that increased protein levels of MTl - MMP may be necessary for this conversion to proceed.This present study documents a role for MTl - MMP in experimental AAA formation, possibly mediated by increased MMP - 2 activation. An understanding of MTl - MMP and its role in AAA may ultimately provide a pharmacologic modality by which to inhibit AAA development and progression in humans.ConclusionThe rodent aortic aneurysm model exhibits upregulation of MTl - MMP expression and protein with subsequent increased MMP - 2 expression and protein, which probablely was of relevance in the pathogenesis of an abdominal aortic aneurysm.
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