BACKGROUND: To characterize the cells responsible for neointima formation after porcine coronary artery wall injury, we studied the expression of smooth muscle cell (SMC) differentiation markers in 2 models: (1) self-expanding stent implantation resulting in no or little interruption of internal elastic lamina and (2) percutaneous transluminal coronary angioplasty (PTCA) resulting in complete medial rupture and exposure of adventitia to blood components. METHODS AND RESULTS: The expression of alpha-smooth muscle (SM) actin, SM myosin heavy chain isoforms 1 and 2, desmin, and smoothelin was investigated by means of immunohistochemistry and Western blots in tissues of the arterial wall collected at different time points and in cell populations cultured from these tissues. The expression of smoothelin, a marker of late SMC differentiation, was used to discriminate between SMCs and myofibroblasts. Both stent- and PTCA-induced neointimal tissues and their cultured cell populations expressed all 4 markers. The adventitial tissue underlying PTCA-induced lesions temporarily expressed alpha-SM actin, desmin, and SM myosin heavy chain isoforms, but not smoothelin. When placed in culture, adventitial cells expressed only alpha-SM actin. CONCLUSIONS: Our results suggest that SMCs are the main components of coronary artery neointima after both self-expanding stent implantation and PTCA. The adventitial reaction observed after PTCA evolves with a chronology independent of that of neointima formation and probably corresponds to a myofibroblastic reaction.