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Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion

Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion
Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion
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.

Methods and 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.
0954-6928
611-621
Mayranpaa, Mikko I.
2070fe52-8bef-4536-b8d2-2235a94af1a0
Heikkila, Hanna M.
4b696bac-4cd0-4061-acdb-d6bb2a1d0d91
Lindstedt, Ken A.
cdb20a95-cbe9-452f-bb44-e10d15ec2867
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Kovanen, Petri T.
882d647a-7ebe-44ef-9c22-eb1f5066efb1
Mayranpaa, Mikko I.
2070fe52-8bef-4536-b8d2-2235a94af1a0
Heikkila, Hanna M.
4b696bac-4cd0-4061-acdb-d6bb2a1d0d91
Lindstedt, Ken A.
cdb20a95-cbe9-452f-bb44-e10d15ec2867
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Kovanen, Petri T.
882d647a-7ebe-44ef-9c22-eb1f5066efb1

Mayranpaa, Mikko I., Heikkila, Hanna M., Lindstedt, Ken A., Walls, Andrew F. and Kovanen, Petri T. (2006) Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion. Coronary Artery Disease, 17 (7), 611-621. (doi:10.1097/01.mca.0000224420.67304.4d).

Record type: Article

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.

Methods and 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.

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Published date: November 2006

Identifiers

Local EPrints ID: 59374
URI: http://eprints.soton.ac.uk/id/eprint/59374
ISSN: 0954-6928
PURE UUID: f62f7847-a5f0-4486-b50f-e59a4f18dc13
ORCID for Andrew F. Walls: ORCID iD orcid.org/0000-0003-4803-4595

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Date deposited: 03 Sep 2008
Last modified: 16 Mar 2024 02:38

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Contributors

Author: Mikko I. Mayranpaa
Author: Hanna M. Heikkila
Author: Ken A. Lindstedt
Author: Andrew F. Walls ORCID iD
Author: Petri T. Kovanen

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