A significant increase in the collagen content and a significant reduction in the elastin content of VV were demonstrated. The net increase in the collagen/elastin ratio is indicative of an imbalance in the connective tissue matrix. The biochemical profile of PV was similar to VV and significantly different from NV. These preliminary data support the presence of connective tissue abnormalities before valvular insufficiency. In addition, the absence of an increase in the proteolytic activity excludes enzymatic matrix degradation as an essential component in the formation of venous varicosities.

A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteo-T he extracellular matrix (ECM) is a complex network of various proteins and proteoglycans maintained by an intricate balance between the synthesis and degradation of its structural components. The maintenance of tissue integrity through remodeling and repair of tissue damage involves the interaction of numerous enzymes and the inhibitors that keep their activity in check. Disturbances in the balance between proteinases and antiproteinases have been implicated in the accelerated degradation of ECM associated with the development of various pathological states, including emphysema and rheumatoid arthritis. 15 Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes with a broad specificity for degrading various ECM components. 6 After secretion in latent form(s), these enzymes are activated; their activation is accompanied by a loss in molecular mass. Their activity is inhibited by specific protein inhibitors called the tissue inhibitors of metalloproteinases (TIMPs). MMP-3, or stromelysin-1, degrades a number of ECM components including proteoglycan, fibronectin, laminin, and gelatin (denatured collagen). MMP-9 (92-kD type IV collagenase) has elastolytic activity in addition © 1994 American Heart Association, Inc.lytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease. to its ability to degrade types IV and V collagen and gelatin. 7 Loss of elastic fibers and disruption of normal matrix structure in the vascular wall are hallmarks of abdominal aortic aneurysm (AAA) disease. Increased elastase, collagenase, and gelatinase activities in the aneurysmal aortic wall have been extensively reported and proposed as mediators of the tissue damage observed. 815 We have...

The results suggest that the latency in AAA formation in this model corresponds with a complex sequence of biochemical and cellular events. The model provides an "early window" into these interesting early phases leading to aneurysm formation.

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