Abstract 2135: Alteration Of Metalloproteinase Expression Profile In Proximal Pulmonary Arterial Wall From Patients With Fallot’S Tetralogy
Matrix metalloproteinases (MMPs) is a family of enzymes for extracellular matrix degradation that has been know to play an important role in the disease-related vascular remodeling, however, its profile in normal pulmonary artery and the role in Fallot’s tetralogy (TOF) have never been characterized in human. We examined the profile of MMPs and their regulatory proteins in proximal pulmonary artery wall (PA) and aortic wall (AO) from 11 patients with TOF who underwent orthotopic heart transplantation. PA and AO walls collected from 11 age and size matched donor hearts were used as control (NC). Protein expression level of MMP1, MMP2, MMP3, MMP9 and MMP13 were determined by quantitative Western Blot analysis. MMP activity was further examined by zymographic analysis. A remarkable increase in both latent and active forms of MMP2 level corresponding to Actin value was found in PA wall of patients with TOF (0.67±0.21 and 0.43±0.18) compared with that in NC (0.28±0.12 and 0.17±0.08, p<0.05). The latent MMP9 level in PA wall was also significantly increased in TOF group (0.42±0.12) compared with that in NC (0.19±0.08, p<0.05), and the enhancement in active form of MMP9 level even greater (0.54±0.16 vs. 0.18±0.07, p<0.05). Interestingly, the level of these two gelatinases in PA wall in TOF was increased and reach to the similar level of that in the wall of ascending AO, that is no difference in TOF (0.44±0.21and 0.38±0.15) and in NC (0.47±0.23 and 0.37±0.14, p>0.05). Zymographic analysis also shows a significant increase of MMP9 activity (95%) and MMP2 activity (75%) in TOF. In contrast, the latent form of MMP1 level was significantly increased, but the active form of MMP1 was only slightly increased in PH. MMP3 level was only slightly increased and MMP13 levels was not changes in PH group. The expression level of MMPs inhibitory proteins, TIMP-1 in PA was decreased 38%±6% in TOF compared with that in NC (p<0.05). TIMP-2 and TIMP-3 expression level in PA and AO was not significantly changed in TOF.
Conclusion: Our results demonstrate that in normal heart MMP2 and MMP9 level in PA are lower than that in aortic wall, but it was significantly increased in TOF patients. This upregulated and aortic-like MMPs profile may play an important role in the degraded matrix in PA from patients with TOF.