title: Alpha-actin isoform distribution in normal and failing human heart: a morphological, morphometric, and biochemical study.
abstract: We investigated the distribution of alpha-skeletal, alpha-cardiac, and alpha-smooth muscle actin isoforms in human heart during development, hypertrophy, and failure. At 20 weeks of fetal life, alpha-skeletal actin was localized in a small proportion of subendocardial and papillary muscle cardiomyocytes. At this gestation time, diffuse alpha-cardiac actin staining was observed, associated with focal expression of alpha-smooth muscle actin. In normal adult subjects, alpha-skeletal actin positive cardiomyocytes were distributed in a transmural gradient with the highest proportion located subendocardially. In myocardial hypertrophy and cardiomyopathies, the amount of alpha-skeletal actin was increased and diffuse staining was seen in all layers of ventricular myocardium, with the exception of idiopathic dilated cardiomyopathies. Cardiomyocytes were negative for alpha-smooth muscle actin in all pathological situations studied. As expected, fibroblasts in post-infarct scars expressed alpha-smooth muscle actin and transforming growth factor-beta1 but, surprisingly, were negative for these proteins in interstitial fibrosis. Our results demonstrate that increased expression of alpha-skeletal actin in the diseased human heart is associated with increased myocyte stretch, increased wall stress, and pressure overload, but not with idiopathic dilated cardiomyopathies. They also suggest that fibrotic changes develop with different mechanisms in scars versus interstitial fibrosis.
authors.affiliation: Department of Pathology, University Hospital Groningen, Groningen, The Netherlands.
authors.forename: Albert J H
authors.initials: AJ
authors.lastname: Suurmeijer
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
authors.forename: Arianna
authors.initials: A
authors.lastname: Francesconi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bocchi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.forename: Luigi Giusto
authors.initials: LG
authors.lastname: Spagnoli
authors.forename: Giulio
authors.initials: G
authors.lastname: Gabbiani
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D000199:Actins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005333:Fetus / Q000378:metabolism; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D000199:Actins; D020033:Protein Isoforms