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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:326.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Phenotypic Modulation of Intima and Media Smooth Muscle Cells in Fatal Cases of Coronary Artery Lesion

Hiroyuki Hao; Giulio Gabbiani; Edoardo Camenzind; Marc Bacchetta; Renu Virmani; Marie-Luce Bochaton-Piallat

From the Department of Pathology and Immunology (G.G., M.B., M.-L.B.-P.), University of Geneva-CMU, Geneva, Switzerland; Department of Pathology (H.H.), Hyogo Medical University, Hyogo, Japan; Division of Cardiology (E.C.), University Hospital Geneva, Geneva, Switzerland; CVPath (R.V.), International Registry of Pathology, Gaithersburg, Md.

Correspondence to Marie-Luce Bochaton-Piallat, University of Geneva-CMU, Department of Pathology and Immunology, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland. E-mail Marie-Luce.Piallat{at}medecine.unige.ch

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 -smooth muscle actin (-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 -SMA was detected in the intima of the different lesions; moreover, -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 -SMA–positive MFs in erosions compared with stable plaques correlates with the higher appearance of thrombotic complications in this situation.

A systematic study of smooth muscle cell (SMC) differentiation marker expression was performed in mildly stenotic plaques, stable plaques, erosions, and restenotic lesions of coronary arteries. An important medial atrophy occurred in restenotic lesions and stable plaques. The dedifferentiated features of intimal SMCs suggest they have modulated into myofibroblasts.

Key Words: -smooth muscle actin • erosion • smooth muscle myosin heavy chains • smoothelin • stable plaque

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