Circulating Biochemical Marker Levels of Collagen Metabolism Are Abnormal in Patients with Abdominal Aortic Aneurysm

Abstract

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.