Phenotypic modulation of intima and media smooth muscle cells in fatal cases of coronary artery lesion

Objectives— Characterize the phenotypic features of media and intima coronary artery smooth muscle cells (SMCs) in mildly stenotic plaques, erosions, stable plaques, and in-stent restenosis. Methods and Results— Expression of α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin was investigated by immunohistochemistry followed by morphometric quantification. The cross-sectional area and the expression of cytoskeletal proteins in the media were lower in restenotic lesions and, to a lesser extent, in stable plaques compared with mildly stenotic plaques and erosions. An important expression of α-SMA was detected in the intima of the different lesions; moreover, α-SMA staining was significantly larger in erosions compared with all other conditions. In the same location, a striking decrease of SMMHCs and a disappearance of smoothelin were observed in all situations. Conclusions— Medial atrophy is prevalent in restenotic lesions and stable plaques compared with mildly stenotic plaques and erosions. Intimal SMCs of all situations exhibit a phenotypic profile, suggesting that they have modulated into myofibroblasts (MFs). The high accumulation of α-SMA–positive MFs in erosions compared with stable plaques correlates with the higher appearance of thrombotic complications in this situation.