Matrix metalloproteinases and tissue inhibitors of metalloproteinases expression in human cerebral ruptured and unruptured aneurysm.

ABSTRACT

BACKGROUND: [corrected] Matrix metalloproteinases and TIMPs are potent elastases and collagenases, which regulate the remodeling of vascular and play an important role in the development of cerebral aneurysm. Until now, little quantitative data regarding MMPs and TIMPs exist. METHODS: Tissue samples of cerebral aneurysm were obtained from 30 patients who underwent cerebral aneurysm clipping operation. We used real-time RT-PCR method to quantitatively measure mRNA levels in small tissue samples and determined gene expression levels of MMPs and TIMPs relative to that of GAPDH in each sample. The ELISA method has been used to measure the serum level of MMP-2 and MMP-9 in patients with cerebral ruptured aneurysm and patients with unruptured aneurysm. RESULT: Matrix metalloproteinase-2 and MMP-9 were overexpressed in cerebral ruptured aneurysm compared with unruptured aneurysm (4.28 +/- 2.01 vs 0.16 +/- 0.12 [P < .01] and 5.21 +/- 0.87 vs 1.69 +/- 1.00 [P < .05], respectively). The expression levels of MMP-2 to TIMP-1, MMP-2 to TIMP-2, MMP-2 to TIMP-3, and MMP-9 to TIMP-2 were higher in cerebral ruptured aneurysms than in unruptured aneurysms (1.22 +/- 0.53 vs 0.18 +/- 0.05, 4.23 +/- 1.32 vs 0.53 +/- 0.12, 1.69 +/- 0.49 vs 0.18 +/- 0.02, and 7.61 +/- 1.61 vs 2.76 +/- 0.76, respectively; P < .05). Patients with cerebral ruptured aneurysm (n = 15) had higher serum MMP-2 and MMP-9 levels than those with unruptured aneurysm detectable by angiography (n = 15) (1047 +/- 33 vs 110 +/- 26 ng/mL and 1066 +/- 43 vs 120 +/- 27 ng/mL, respectively; P < .02). CONCLUSION: The disproportional expression of among MMP-2, MMP-9, and TIMP contribute to the evolution of cerebral aneurysm. Real-time RT-PCR method is suitable for the determination of mRNA levels in small samples of vascular tissue.