title: Human activin-A is expressed in the atherosclerotic lesion and promotes the contractile phenotype of smooth muscle cells.
abstract: Activin is a member of the transforming growth factor-beta superfamily, and it modulates the proliferation and differentiation of various target cells. In this study, we investigated the role of activin in the initiation and progression of human atherosclerosis. The expression of activin, its physiological inhibitor follistatin, and activin receptors were assayed in human vascular tissue specimens that represented various stages of atherogenesis. In situ hybridization experiments revealed activin mRNA in endothelial cells and macrophages and a strong induction of activin expression in neointimal smooth muscle cells from the early onset of atherogenesis. We developed an "in situ free-activin binding assay" by using biotinylated follistatin, which allowed us to detect bioactive activin at specific sites in atherosclerotic lesions. The mRNAs encoding the activin receptors are expressed similarly in normal and atherosclerotic tissue, which indicates that activin-A signaling in atherogenesis is most likely dependent on changes in growth factor concentrations rather than on receptor levels. In vitro, activin induces the contractile, nonproliferative phenotype in cultured smooth muscle cells, as is reflected by increased expression of smooth muscle-specific markers (SMalpha-actin and SM22alpha). Our data provide evidence that activin induces redifferentiation of neointimal smooth muscle cells, and we hypothesize that activin is involved in plaque stabilization.
authors.affiliation: Academic Medical Center, University of Amsterdam, Department of Biochemistry, Amsterdam and Erasmus University, Department of Endocrinology and Reproduction, Rotterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Engelse
authors.forename: J M
authors.initials: JM
authors.lastname: Neele
authors.forename: T A
authors.initials: TA
authors.lastname: van Achterberg
authors.forename: B E
authors.initials: BE
authors.lastname: van Aken
authors.forename: R H
authors.initials: RH
authors.lastname: van Schaik
authors.forename: H
authors.initials: H
authors.lastname: Pannekoek
authors.forename: C J
authors.initials: CJ
authors.lastname: de Vries
mesh_terms: D000199:Actins / Q000235:genetics; D029404:Activin Receptors; D028341:Activins; D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics; D014661:Vasoconstriction / Q000235:genetics
chemical_list: D000199:Actins; D038681:Follistatin; D006023:Glycoproteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C058992:Tagln protein, mouse; C051615:transgelin; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors