Dexamethasone arterializes venous endothelial cells by inducing mitogen-activated protein kinase phosphatase-1: a novel antiinflammatory treatment for vein grafts?
BACKGROUND
Vein grafting in coronary artery surgery is complicated by a high restenosis rate resulting from the development of vascular inflammation, intimal hyperplasia, and accelerated atherosclerosis. In contrast, arterial grafts are relatively resistant to these processes. Vascular inflammation is regulated by signaling intermediaries, including p38 mitogen-activated protein (MAP) kinase, that trigger endothelial cell (EC) expression of chemokines (eg, interleukin-8, monocyte chemotactic protein-1) and other proinflammatory molecules. Here, we have tested the hypothesis that p38 MAP kinase activation in response to arterial shear stress (flow) may occur more readily in venous ECs, leading to greater proinflammatory activation.


RESULTS
Comparative reverse-transcriptase polymerase chain reaction and Western blotting revealed that arterial shear stress induced p38-dependent expression of monocyte chemotactic protein-1 and interleukin-8 in porcine jugular vein ECs. In contrast, porcine aortic ECs were protected from shear stress-induced expression of p38-dependent chemokines as a result of rapid induction of MAP kinase phosphatase-1. However, we observed with both cultured porcine jugular vein ECs and perfused veins that venous ECs can be protected by brief treatment with dexamethasone, which induced MAP kinase phosphatase-1 to suppress proinflammatory activation.


CONCLUSIONS
Arterial but not venous ECs are protected from proinflammatory activation in response to short-term exposure to high shear stress by the induction of MAP kinase phosphatase-1. Dexamethasone pretreatment arterializes venous ECs by inducing MAP kinase phosphatase-1 and may protect veins from inflammation.
British Heart Fund Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.
Mustafa
M
Zakkar
Le Anh
le A
Luong
Hera
H
Chaudhury
Oeyvind
O
Ruud
Prakash P
PP
Punjabi
Jon R
JR
Anderson
John W
JW
Mullholand
Anne T
AT
Clements
Rob
R
Krams
Nicholas
N
Foin
Thanos
T
Athanasiou
Edward L S
EL
Leen
Justin C
JC
Mason
Dorian O
DO
Haskard
Paul C
PC
Evans
D000818:Animals; D000893:Anti-Inflammatory Agents; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D020011:Protective Agents; D013552:Swine; D015533:Transcriptional Activation / Q000187:drug effects; D014680:Veins / Q000187:drug effects / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D020011:Protective Agents; D003907:Dexamethasone; D019950:Mitogen-Activated Protein Kinase 1