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(Circulation Research. 2007;100:1055.)
© 2007 American Heart Association, Inc.

Cellular Biology

Intimal Smooth Muscle Cells of Porcine and Human Coronary Artery Express S100A4, a Marker of the Rhomboid Phenotype In Vitro

Anne C. Brisset, Hiroyuki Hao, Edoardo Camenzind, Marc Bacchetta, Antoine Geinoz, Jean-Charles Sanchez, Christine Chaponnier, Giulio Gabbiani, Marie-Luce Bochaton-Piallat

From the Department of Pathology and Immunology (A.C.B., M.B., A.G., C.C., G.G., M.-L.B.-P.), University of Geneva, Switzerland; Department of Surgical Pathology (H.H.), Hyogo College of Medicine, Japan; Division of Cardiology (E.C.) and Central Clinical Chemistry Laboratory (J.-C.S.), University Hospital of Geneva, Switzerland.

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

We reported that smooth muscle cell (SMC) populations isolated from normal porcine coronary artery media exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). R-SMCs are recovered in higher proportion from stent-induced intimal thickening compared with media suggesting that they participate in intimal thickening formation. Our aim was to identify a marker of R-SMCs in vitro and to explore its possible expression in vivo. S- and R-SMC protein extracts were compared by means of 2-dimensional polyacrylamide gel electrophoresis followed by tandem mass spectrometry. S100A4 was found to be predominantly expressed in R-SMC extracts. Using a monoclonal S100A4 antibody we confirmed that S100A4 is highly expressed by R-SMCs and hardly detectable in S-SMCs. S100A4 was colocalized with -smooth muscle actin in stress fibers of several quiescent cells and upregulated during migration. PDGF-BB, FGF-2 or coculture with endothelial cells, which modulate S-SMCs to a R-phenotype, increased S100A4 expression in both S- and R-SMCs. Silencing of S100A4 mRNA in R-SMCs decreased cell proliferation, suggesting a functional role for this protein. In vivo S100A4 was absent in normal porcine coronary artery media, but highly expressed by SMCs of stent-induced intimal thickening. In humans, S100A4 was barely detectable in coronary artery media and markedly expressed in SMCs of atheromatous and restenotic coronary artery lesions. Our results indicate that S100A4 is a marker of porcine R-SMCs in vitro and of intimal SMCs during intimal thickening development. It is also a marker of a large population of human atheromatous and restenotic SMCs. Clarifying S100A4 function might be useful to understand the evolution of atherosclerotic and restenotic processes.

Key Words: 2D-PAGE • stent • endothelial cells • mts1 • -smooth muscle actin • smoothelin

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