MMP inhibition and lumen loss after balloon angioplasty or stenting.

Abstract

To the Editor: With interest we read the paper by Cherr et al1 reporting the negligible effect of matrix metalloproteinase (MMP) inhibition on constrictive remodeling and intimal hyperplasia after balloon angioplasty and stenting, respectively. As the authors mentioned, the results are at odds with observations from several published studies that have reported a significant reduction of late lumen loss after intervention by MMP inhibition.2-4⇓⇓ Several possible explanations were proposed to account for these differences, including route of administration and lack of activity of the compound used by Cherr et al1 against tumor necrosis factor-α–converting enzyme and MMP-1. However, other explanations for these controversial results may be considered. First, we agree with the authors that the spectrum of MMP inhibitory activity, and thus clinical effects, may significantly differ among compounds. Marimastat and GM6001 are two nonspecific MMP inhibitors with potent inhibitory MMP-1 activity that have been shown to inhibit constrictive remodeling after balloon angioplasty and in-stent intimal hyperplasia, respectively. This result may point to an important role for the breakdown of intact collagen fibers in subsequent response to injury. However, we feel that the route of administration cannot adequately explain the observed differences among studies. Significant inhibition of constrictive remodeling after balloon injury was achieved by both oral3 and parenteral2 preparations whereas subcutaneous delivery of GM6001 significantly inhibited in-stent intimal hyerplasia.4 Second, we feel that differences in animal models may also explain the lack of inhibitory effect on post-angioplasty constrictive remodeling in the study by Cherr et al.1 In an earlier publication, Geary et …