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Calmodulin expression distinguishes the smooth muscle cell population of human carotid plaque

Marchetti, Giovanna
Palagi, Patricia M
Zerbinati, Carlotta
Guastella, Giuseppe
Gagliano, Teresa
Bernardi, Francesco
Mascoli, Francesco
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Published in The American journal of pathology. 2013, vol. 183, no. 3, p. 996-1009
Abstract Several observations suggest the expansion of a distinct medial smooth muscle cell (SMC) subset in atherosclerosis and restenosis. We characterized the phenotypic features of SMC subsets in cultures derived from human carotid endarterectomy specimens. Specimens comprised an undiseased portion (thin intimal thickening with the underlying media) and a diseased portion (atherosclerotic plaque with the underlying media). From plaque tissues of the diseased portion, only macrophage-derived foam cells were retrieved. From medial tissues, two SMC phenotypes were isolated: large SMCs (flat with a monolayered growth pattern, from the undiseased portion) and small SMCs (fusiform and growing in multilayers, from the undiseased and diseased portions after co-culture with macrophage-derived foam cells). Small SMCs displayed higher proliferative and migratory activities and were less differentiated than large SMCs. Proteomic analysis showed that calmodulin was predominant in small SMCs. Co-culture of large SMCs with macrophage-derived foam cells induced a transition to the small phenotype with increased calmodulin expression. The calmodulin inhibitor W-7 decreased the proliferation of small SMCs and prevented the large to small phenotypic transition. In vivo, calmodulin was markedly expressed in SMCs of atherosclerotic plaques and was barely detectable in the media. Macrophage-derived foam cells promote selective migration from the media of atheroma-prone SMCs characterized by calmodulin overexpression. Further studies of small SMCs could be instrumental in understanding atherosclerosis pathogenesis and in planning therapeutic strategies.
Keywords Calmodulin/antagonists & inhibitors/genetics/metabolismCarotid Arteries/drug effects/metabolism/pathologyCell Proliferation/drug effectsCell SeparationCell SizeCulture Media, Conditioned/pharmacologyEndarterectomy, CarotidGene Expression Regulation/drug effectsHumansImmunohistochemistryMacrophages/drug effects/metabolism/pathologyMyocytes, Smooth Muscle/drug effects/metabolism/pathologyPhenotypePlaque, Atherosclerotic/genetics/pathologyProteomicsProto-Oncogene Proteins c-sis/pharmacologyRNA, Messenger/genetics/metabolismSulfonamides/pharmacology
PMID: 23838429
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Research group Bochaton-Piallat Marie-Luce (pathologie et immunologie) (646)
Swiss National Science Foundation: 310030_130700
Swiss National Science Foundation: 310030_146790
Autre: Fondation Artères, Fondation Gustave et Simone Prévot, Jubiläumsstiftung Swiss life, Novartis Foundation for Medicine and Biology grant 06C82; Fondazione Cassa di Risparmio di Ferrara; Ministero Istruzione Università Ricerca; Fondation Ernst and Lucie Schmidheiny; Fondazione Italiana Sclerosi Multipla (Cod.297/10/F1)
(ISO format)
COEN, Matteo et al. Calmodulin expression distinguishes the smooth muscle cell population of human carotid plaque. In: The American journal of pathology, 2013, vol. 183, n° 3, p. 996-1009. doi: 10.1016/j.ajpath.2013.06.006 https://archive-ouverte.unige.ch/unige:41353

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Deposited on : 2014-10-30

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