title: Smooth muscle-like cells resident in the media participate in spasm-induced coronary intimal hyperplasia.
abstract: BACKGROUND
  Coronary intimal hyperplasia occurs at the site of spasm in patients with vasospastic angina. The migration of vascular smooth muscle cells (VSMCs) from the media has been proposed as a potential mechanism; however, this has not been confirmed with supportive evidence.
  
  
  OBJECTIVE
  To determine which cell types participate in spasm-induced coronary intimal hyperplasia.
  
  
  METHODS
  Morphological changes in spastic coronary artery segments in beagles were examined using electron microscopy and immunohistochemical staining of cell markers at 1 h, 3 h and 6 h, and two and four weeks after spasm provocation.
  
  
  RESULTS
  Small smooth muscle-like cells (SMLCs) were observed in the media of nonspastic coronary segments using electron microscopy. These cells attached side-to-side to large, known VSMCs. At 1 h to 6 h after spasm provocation, SMLCs separated from VSMCs, changed to an amoebic configuration and migrated through cleaved junctions or disrupted portions of the internal elastic lamina into the subendothelial space. The SMLCs expressed alpha-smooth muscle actin and N-cadherin, but not smooth muscle myosin heavy chain-1 and β-actin, suggesting that they were myofibroblasts and not a synthetic phenotype of VSMCs. Intimal hyperplasia was observed in all preparations at two and four weeks after spasm provocation. Furthermore, alpha-smooth muscle actin-positive SMLCs, often amoebic in configuration, were observed in the hyperplastic intima.
  
  
  CONCLUSIONS
  On coronary spasm provocation, SMLCs (ie, possible myofibroblasts) resident in the media migrate as a spearhead into the intima and play a role in coronary intimal hyperplasia.
authors.affiliation: Department of Pathology, Toho University Medical Center Sakura Hospital, Sakura, Japan;
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hiruta
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Uchida
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Uchida
keywords: Alpha-smooth muscle actin; Coronary spasm; Migration; Myofibroblasts; Vascular smooth muscle-like cells