Homocysteine and metalloprotease-3 and -9 in patients with ascending aorta aneurysms

Abstract

Introduction: Matrix metalloprotease (MMP) activity is increased in ascending and abdominal aortic aneurysms. Elevated plasma homocysteine (Hc) levels have been reported in patients with abdominal aneurysms. However, there are no published reports correlating, Hc and MMP levels in patients with ascending aortic aneurysms (AAAs).

Materials and methods: This study attempts to determine whether serum or tissue Hc in patients undergoing surgery for AAAs is associated with aneurysm diameter, circulating and tissue levels of MMP-3 and MMP-9 assessed by Enzyme-linked immunosorbent assay (ELISA) and their mRNA tissue expression assessed by real-time PCR. Twenty-seven patients were recruited in the study.

Results: Forty-three percent of the patients had abnormal Hc serum levels (>35.9 μmol/L). Circulating MMP-3 (6.44±4.20 ng/mL) and MMP-9 levels (134±11.4 ng/mL) were elevated compared to healthy controls (p<0.001). Positive correlations were observed between circulating MMP-9, tissue MMP-3 and MMP-9 concentrations with serum Hc (r=0.773, p=0.011; r=0.461, p=0.014; r=0.526, p=0.024, respectively). MMP-9 mRNA was expressed in 21% of the aneurysms. No MMP-3 mRNA expression was detected in the studied specimens. A negative correlation between tissue Hc and aneurysm diameter was detected. No associations of serum Hc, MMP-3 and MMP-9 levels in both serum and tissue with aneurysm diameter were noted.

Conclusion: Our results suggest that Hc, even in patients with mild hyperhomocysteinaemia, is involved in the pathophysiology of AAA, through the regulation of MMP-3 and MMP-9 activity.