Hideshi Okada1, Genzou Takemura2, Hiromitsu Kanamori1, Akiko Tsujimoto1, Kazuko Goto1, Itta Kawamura1, Takatomo Watanabe1, Kentaro Morishita1, Nagisa Miyazaki1, Toshiki Tanaka1, Hiroaki Ushikoshi1, Masanori Kawasaki1, Tatsuhiko Miyazaki1, Natsuko Suzui1, Kazuhiko Nishigaki1, Atsushi Mikami1, Shinji Ogura1, Shinya Minatoguchi1. 1. 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.). 2. 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.
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. METHODS AND 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.
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. METHODS AND 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.