Background: Wound healing at the site of medial injury after percutaneous transluminal coronary angioplasty (PTCA) is dominated by smooth muscle cells. This reaction may also cause restenosis. Division and migration of smooth muscle cells relate closely to their cytoskeletal features, as shown experimentally, but in humans little information is available regarding smooth muscle cell activity in post-angioplasty coronary arteries.
Materials and methods: This study is based on eight dilated coronary arteries obtained at autopsy from six patients who died within 4 months of an initially successful PTCA. In each patient, a single PTCA had been performed and the target site was identified, sectioned serially, and studied with conventional and immunohistochemical techniques.
Results: All target sites showed laceration extending into the media. Two days after PTCA the site of injury was covered by a fibrin-platelet thrombus. The smooth muscle cells of the pre-existent media, immediately adjacent to the site of injury, showed loss of staining for both muscle actin and smooth muscle cell actin, using the antibodies HHF-35 (an anti-muscle actin marker) and CGA-7 (an anti-smooth muscle cell actin marker), respectively. Five days after PTCA, this area had expanded; a distinct influx of macrophages was apparent. From 12 days onwards, the staining density with HHF-35 in the pre-existent media increased and was almost restored to normal at 20 days, but staining with CGA-7 was retarded until approximately 4 months after PTCA. In the repair tissue, spindle-shaped cells were first seen 5 days after PTCA. These cells stained positive with vimentin but did not stain with either actin marker. Macrophages were present at this stage. At 12 days after PTCA, some spindle-shaped cells stained positive with HHF-35, but all were negative with CGA-7. At 16 days, the staining density with HHF-35 had increased, but CGA-7 was still negative. At 20 days, the maximal staining density with HHF-35 was obtained. The vast majority of spindle-shaped cells also stained positive with CGA-7 4 months after PTCA. Endothelial cells on the luminal surface were first identified 4 months after PTCA.
Conclusion: The observations provide support that cytoskeletal changes observed experimentally also play a role in human coronary arteries after PTCA. De-differentiation of smooth muscle cells of the pre-existent media, preceding a noticeable cellular response, appears to be a fundamental process.