Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment

Objectives The goal of this study was to evaluate the cellular and extracellular composition of human coronary arterial in-stent restenosis after various periods of time following stent deployment. Background Neointimal in-growth rather than stent recoil is thought to be important for coronary arterial in-stent restenosis. There is only limited data on the cellular and extracellular composition changes with time after stent deployment. Methods We analyzed 29 coronary arterial in-stent restenotic tissue samples (14 left anterior descending coronary artery, 10 right coronary artery, and 5 left circumflex artery) retrieved by using directional coronary atherectomy from 25 patients at 0.5 to 23 (mean, 5.7) months after deployment of Palmaz-Schatz stents employing histochemical and immunocytochemical techniques. Results Cell proliferation was low (0% to 4%). Myxoid tissue containing extracellular matrix (ECM) enriched with proteoglycans was found in 69% of cases and decreased over time after stenting. Cell-depleted areas were found in 57% of cases and increased with time after stenting. Versican, biglycan, perlecan, and hyaluronan were present with varying individual distributions in all samples. Positive transforming growth factor-β1 staining was found in 80% of cases. Immunostaining with alpha-smooth muscle actin identified the majority of cells as smooth muscle cells with occasional macrophages present (≤12 cells per section). Conclusions These data suggest that enhanced ECM accumulation rather than cell proliferation contribute to later stages of in-stent restenosis. Balloon angioplasty of in-stent restenosis may, therefore, fail due to ECM changes during: 1) additional stent expansion, 2) tissue extrusion out of the stent, or 3) tissue compression.