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

Abstract

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 crosssectional 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. Key Words: ␣-smooth muscle actin Ⅲ erosion Ⅲ smooth muscle myosin heavy chains Ⅲ smoothelin Ⅲ stable plaque T hrombosis after plaque rupture is the most frequent cause of coronary mortality, followed by thrombosis over an erosion, whereas a smaller but significant proportion of deaths corresponds to the presence of stable plaques without evidence of thrombosis. 1 Several factors have been suggested to participate in the mechanisms of plaque rupture such as altered matrix turnover and blood rheology, increased coagulation, and recurrent infections. 2 Macrophages and T lymphocytes are increased at site of plaque rupture, whereas erosions and stable plaques contain relatively few inflammatory cells. Conclusions-Medial

Tissue stiffness, latent TGF-β1 Activation, and mechanical signal transduction: Implications for the pathogenesis and treatment of fibrosis

“…Generation of fi broblasts and myofi broblasts by epithelial to mesenchymal transition was further demonstrated during tumor development and fi brosis of lung, heart, and liver [16,17]. During vessel repair and dermal scarring in SSc, pericytes have been shown to attain contractile myofi broblast features [18], and dedifferentiation of smooth muscle cells contributes to the generation of myofi broblasts in atheromatous plaques [5].…”

“…It is the high contractile activity of the myofibroblast that generates connective tissue contracture and irreversible ECM remodeling, producing a stiff fi brotic scar. Formation of fi brotic tissue after injury can affect almost all organs, including skin [3], heart [4], vasculature [5], liver [6], lung [7], and kidney [8]. Cancer cells stimulate the formation of scar-like connective tissue and hijack this complex environment to promote tumor progression [9].…”

Smooth muscle cells of human intracranial aneurysms assume phenotypic features similar to those of the atherosclerotic plaque

“…Immunostaining for α-SMA, SMMHCs, S100A4, and CD68 were performed on adjacent sections. For image analysis quantification (see below), time of antibody incubation and chromogen development were scrupulously standardized, and for a given antibody, all sections were processed simultaneously [6]. Before using the first antibody, immunoreactivity was intensified by microwave treatment (750 W, 5 min) in citrate buffer (10 mM, pH 6.0) for α-SMA and CD68, and by pressure cooker treatment (3 min) in citrate buffer for SMMHCs and S100A4.…”

“…Quantitative immunohistochemistry was performed as previously described [6]. Slides for morphometric analysis (n=11) were scanned at 20× magnification and high resolution using a fully automated Mirax Virtual Slide Scanner equipped with a Plan-Apochromat 20×/ 0.8 objective (Carl Zeiss, Jena, Germany).…”

“…As differentiation markers, we used the cytoskeletal proteins α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin [6]. In addition, S100A4, a calciumbinding protein recently described as a suitable marker of dedifferentiated intimal SMCs in atherosclerotic plaques and restenotic lesions, was also assessed [7].…”