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Matrix metalloproteinase expression in the coronary circulation induced by coronary angioplasty
Yukihiro Hojo1, Uichi Ikeda, Taka aki Katsuki
1Department of Cardiology, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498, Japan.
Abstract:
Recent studies have revealed that matrix metalloproteinases (MMPs) play an important role in cardiovascular remodeling by degrading the extracellular matrix. We investigated changes in the expression of MMPs due to percutaneous transluminal coronary angioplasty (PTCA). We studied 47 patients with ischemic heart disease who underwent elective PTCA on isolated stenotic lesion of left coronary arteries. Twelve patients received conventional balloon angioplasty, 14 percutaneous transluminal rotational atherectomy and 21 stent implantation. Blood samples were drawn from the coronary sinus immediately before and after, as well as 4 and 24 h, after PTCA. Plasma levels of MMP-1, MMP-2, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 were measured by enzyme-linked immunosorbent assay. Plasma MMP-2 activity was determined with the digestion of a specific chromogenic peptide substrate. We could observe serial changes in plasma MMP-1 levels in the coronary circulation only in one patient, because MMP-1 levels were lower than the limit of detection in other patients. On the other hand, plasma MMP-2 levels in the coronary sinus were detectable in all subjects and increased significantly 4 and 24 h after PTCA. Plasma TIMP-1 levels also showed significant increases 4 and 24 h after PTCA, whereas TIMP-2 did not show significant changes. Plasma MMP-2/TIMP-2 ratio and MMP-2 activity in the coronary sinus showed significant increases 4 and 24 h after PTCA. A positive correlation was observed between MMP-2 levels in the coronary sinus 4 h after PTCA and late loss index 6 months after PTCA. MMP-2 levels in the coronary sinus blood were significantly higher in patients with late restenosis than in those without restenosis. PTCA induces increases in plasma MMP-2 levels and activity in the coronary circulation, which may contribute to vascular remodeling and late restenosis after PTCA.
Insights
Percutaneous transluminal coronary angioplasty (PTCA) increases matrix metalloproteinase-2 (MMP-2) levels and activity in coronary circulation. Elevated MMP-2 correlates with restenosis, suggesting a role in vascular remodeling after PTCA.
Area of Science:
- Cardiovascular Biology
- Interventional Cardiology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are crucial for extracellular matrix remodeling in cardiovascular disease.
- Understanding MMP expression changes post-Percutaneous Transluminal Coronary Angioplasty (PTCA) is vital for managing cardiovascular remodeling.
Purpose of the Study:
- To investigate the impact of PTCA on the expression and activity of MMPs and their inhibitors in patients with ischemic heart disease.
- To determine the relationship between MMP-2 changes and late restenosis following PTCA.
Main Methods:
- Studied 47 patients undergoing elective PTCA for coronary artery stenosis.
- Measured plasma levels of MMP-1, MMP-2, TIMP-1, and TIMP-2 via ELISA in coronary sinus blood before and after PTCA (4 and 24h).
- Assessed MMP-2 activity and MMP-2/TIMP-2 ratio, correlating findings with late loss index and restenosis.
Main Results:
- Plasma MMP-2 levels and activity significantly increased 4 and 24 hours post-PTCA.
- Plasma TIMP-1 levels also increased, while TIMP-2 showed no significant change.
- Elevated MMP-2 levels post-PTCA correlated positively with late loss index and were higher in patients with restenosis.
Conclusions:
- PTCA induces significant increases in MMP-2 levels and activity within the coronary circulation.
- These MMP-2 changes are implicated in vascular remodeling and may contribute to the development of late restenosis after PTCA.