title: Phenotype and physiological significance of the endocardial smooth muscle cells in human failing hearts.
abstract: BACKGROUND
  Extravascular smooth muscle cells are often observed in the endocardium of human failing hearts. Here, we characterized the phenotype of those cells and investigated their physiological significance.
  
  
  RESULTS
  We examined left ventricular biopsy specimens obtained from 44 patients with dilated cardiomyopathy and 6 nonfailing hearts. In Masson trichrome-stained histological preparations, bundles of smooth muscle cells were seen localized in the endocardium in 23 of the 44 specimens (none of the 6 controls). These cells were immunopositive for α-smooth muscle actin, type 2 smooth muscle myosin, desmin, and calponin, but were negative for embryonic smooth muscle myosin, vimentin, fibronectin, and periostin. This profile is indicative of a late differentiation (contractile) smooth muscle phenotype. Electron microscopy confirmed that phenotype, revealing the cells to contain abundant myofilaments with dense bodies but little rough endoplasmic reticulum or Golgi apparatus. In the endocardial smooth muscle-positive group, the left ventricular end-systolic volume index (73±34 versus 105±50 mL/m(2); P=0.021), left ventricular peak wall stress (164±47 versus 196±43 dynes 10(3)/cm(2); P=0.023), and left ventricular end-systolic meridional wall stress (97±38 versus 121±37 dynes 10(3)/cm(2); P=0.036) were all significantly smaller, and the ejection fraction was larger (41±8.8 versus 33±9.3%; P=0.005) than in the endocardial smooth muscle-negative group. However, no histological parameters differed between the 2 groups.
  
  
  CONCLUSIONS
  Endocardial smooth muscle cell bundles in hearts with dilated cardiomyopathy exhibit a mature contractile phenotype and may play a compensatory role mitigating heart failure by reducing left ventricular wall stress and systolic dysfunction.
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Hideshi
authors.initials: H
authors.lastname: Okada
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.). gt@dent.asahi-u.ac.jp.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsujimoto
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Kazuko
authors.initials: K
authors.lastname: Goto
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Takatomo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Kentaro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Nagisa
authors.initials: N
authors.lastname: Miyazaki
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ushikoshi
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Natsuko
authors.initials: N
authors.lastname: Suzui
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishigaki
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mikami
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.affiliation: From the Departments of Emergency and Disaster Medicine (H.O., K.M., H.U., S.O.) and Cardiology (H.K., A.T., K.G., I.K., T.W., N.M., T.T., M.K., K.N., A.M., S.M.), Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University, Mizuho, Japan (G.T.); and Division of Pathology, Gifu University Hospital, Gifu, Japan (T.M., N.S.).
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D017023:Coronary Angiography; D018450:Disease Progression; D004452:Echocardiography; D004699:Endocardium / Q000648:ultrastructure*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009200:Myocardial Contraction; D032389:Myocytes, Smooth Muscle / Q000502:physiology* / Q000648:ultrastructure; D010641:Phenotype; D012189:Retrospective Studies; D013318:Stroke Volume; D016277:Ventricular Function, Left / Q000502:physiology*; D055815:Young Adult
keywords: biopsy; cardiomyopathy, dilated; heart failure; myocytes, smooth muscle; ultrastructure