BACKGROUND: Vascular wall remodeling is a major factor contributing to restenosis after angioplasty that involves migration and proliferation of vascular smooth muscle cells. The release of matrix-degrading metalloproteinases, including metalloproteinase-2 and metalloproteinase-9, facilitates remodeling. Experimental data suggest that nitric oxide (NO) decreases the activity of metalloproteinases and this may attenuate arterial remodeling after balloon injury. We investigated whether metalloproteinase-2, metalloproteinase-9 and NO are released into the coronary sinus blood during angioplasty in coronary patients. METHODS: In 10 patients with stable angina undergoing elective percutaneous transluminal coronary angioplasty of an isolated stenosis of the proximal left anterior descending coronary artery, blood was sampled from the coronary sinus at baseline, immediately and 1 min after each balloon deflation. Plasma release of metalloproteinase-2 and metalloproteinase-9 was assayed by their gelatinolytic activity using zymography, while the liberation of NO metabolites was measured by high-performance liquid chromatography. RESULTS: Two consecutive balloon inflations each of 60 s duration, resulted in an immediate increase (P<0.05) of metalloproteinase-9, but not metalloproteinase-2 activity, followed by normalization of metalloproteinase-9 levels to the baseline within 1 min. Plasma levels of NO metabolites remained unchanged. CONCLUSIONS: Rapid release of metalloproteinase-9 after balloon inflation may both contribute to remodeling and protect the vascular wall from post-angioplasty thrombosis.
BACKGROUND: Vascular wall remodeling is a major factor contributing to restenosis after angioplasty that involves migration and proliferation of vascular smooth muscle cells. The release of matrix-degrading metalloproteinases, including metalloproteinase-2 and metalloproteinase-9, facilitates remodeling. Experimental data suggest that nitric oxide (NO) decreases the activity of metalloproteinases and this may attenuate arterial remodeling after balloon injury. We investigated whether metalloproteinase-2, metalloproteinase-9 and NO are released into the coronary sinus blood during angioplasty in coronary patients. METHODS: In 10 patients with stable angina undergoing elective percutaneous transluminal coronary angioplasty of an isolated stenosis of the proximal left anterior descending coronary artery, blood was sampled from the coronary sinus at baseline, immediately and 1 min after each balloon deflation. Plasma release of metalloproteinase-2 and metalloproteinase-9 was assayed by their gelatinolytic activity using zymography, while the liberation of NO metabolites was measured by high-performance liquid chromatography. RESULTS: Two consecutive balloon inflations each of 60 s duration, resulted in an immediate increase (P<0.05) of metalloproteinase-9, but not metalloproteinase-2 activity, followed by normalization of metalloproteinase-9 levels to the baseline within 1 min. Plasma levels of NO metabolites remained unchanged. CONCLUSIONS: Rapid release of metalloproteinase-9 after balloon inflation may both contribute to remodeling and protect the vascular wall from post-angioplasty thrombosis.
Authors: Ada W Y Chung; Anna Radomski; David Alonso-Escolano; Paul Jurasz; Michael W Stewart; Tadeusz Malinski; Marek W Radomski Journal: Br J Pharmacol Date: 2004-11-08 Impact factor: 8.739