title: Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion.
abstract: OBJECTIVE
  Endothelial erosion has emerged as an important contributor to the pathogenesis of atherosclerosis and its complications, but the molecular mechanisms have remained unclear. As activated mast cells capable of secreting neutral proteases are present in the intima of eroded coronary plaques, we investigated their potential roles in endothelial erosion.
  
  
  RESULTS
  Studies involving double immunostaining of mast cells (tryptase(pos) cells) and platelets (CD42b) in human coronary artery specimens indicated that the number of subendothelial mast cells correlated with the number of parietal microthrombi (P=0.001, rs 0.27). The number of parietal microthrombi was significantly higher (P<0.001) in areas of plaques than in areas of healthy intima. Of the microthrombi 86% were in the lesional coronary segments, of all subendothelial mast cells 15% were located under parietal microthrombi, and of all parietal microthrombi 49% were located over subendothelial mast cells. Double immunostaining revealed the mast cell to neutrophil ratio in the human coronary artery intima to be 5 : 1, and that mast cells are a major local source of cathepsin G. Scanning electron and light microscopy indicated that treatment of fresh human coronary arteries intraluminally with recombinant human (rh)-tryptase and rh-chymase induced endothelial damage characterized by retraction of endothelial cells, disruption of endothelial cell to cell adhesions and desquamation of endothelial cells. VE-cadherin and fibronectin, which are necessary for cell-cell interactions and endothelial cell adhesion, were degraded by tryptase and chymase and also by cathepsin G.
  
  
  CONCLUSIONS
  Activated subendothelial mast cells may contribute to endothelial erosion by releasing proteases capable of degrading VE-cadherin and fibronectin.
authors.affiliation: Wihuri Research Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Mäyränpää
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Heikkilä
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Walls
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D010450:Endopeptidases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D010450:Endopeptidases; D005353:Fibronectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5