Metalloproteinases, insulin-like growth factor-I and its binding proteins in aortic aneurysm.

Abstract

Abdominal aortic aneurysm is accompanied by the impairment of collagen metabolism in arterial wall. Metalloproteinases and collagen-stimulating factors play an important role in the maintenance of balance between collagen biosynthesis and degradation in tissues. Insulin-like growth factor-I (IGF-I) plays a major role in the stimulation of collagen biosynthesis. Its activity and bioavailability to target cells are modulated by IGF binding proteins (IGFBPs). The potential role of these factors in the mechanism of collagen metabolism deregulation in aortic aneurysm is the purpose of this study. Therefore, we have compared the content of collagen, gelatinolytic activity, IGF-I, IGFBP-1 and IGFBP-3 in normal human aorta and aortic aneurysm. The content of hydroxyproline (representing collagen content) in the proteins of aortic aneurysm was found to be similar to that found in normal aorta. Taking into account that some of the hydroxyproline may be derived from collagen degradation products (CDPs), they were separated and hydroxyproline was determined. It has been found that CDP-derived hydroxyproline content in aortic aneurysm was increased as compared with normal aorta, suggesting an increased collagen degradation. In contrast, zymography showed a decrease of collagenolytic activity in aortic aneurysm tissue, but an increase in mural thrombus, compared to respective controls. IGF-I concentration in aortic aneurysm was decreased, while the concentrations of BP-1 and BP-3 were both increased compared to control. The data suggest that increased collagen degradation in aortic aneurysm is due to the increase in collagenolytic activity in mural thrombus accompanying aneurysm tissue. It suggests that the mural thrombus may play a critical role in the pathogenesis of abdominal aortic aneurysm.