Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice.
OBJECTIVE
The aim of this study was to assess whether the anti-inflammatory agent dexamethasone can inhibit vein graft thickening without the occurrence of serious side effects.


METHODS
Venous interposition grafting was performed in the common carotid artery of hypercholesterolemic ApoE3Leiden transgenic mice. Mice were treated with dexamethasone (0.15 mg.kg(-1).d(-1) orally), and after 28 days, vein graft thickening was quantified.


RESULTS
Treatment with dexamethasone resulted in a significant 43% reduction in lesion area without changes in lesion composition when compared with nontreated controls. However, dexamethasone, when administered for a prolonged period of time, is known for its potentially serious side effects. To overcome these potential side effects of prolonged dexamethasone treatment, the effect of a short-term 7-day dexamethasone treatment was studied. This short dexamethasone treatment resulted in a 49% decrease of vein graft thickening at 28 days. Furthermore, it was demonstrated that dexamethasone treatment led to reduced local expression of several proinflammatory cytokines and factors in the vein grafts 24 hours after surgery. Finally, observations in mice were verified in human saphenous organ cultures. Exposure to dexamethasone for either 7 or 28 days significantly reduced intimal hyperplasia formation on cultured saphenous vein segments.


CONCLUSIONS
Short-term anti-inflammatory treatment with dexamethasone leads to a significant reduction in vein graft thickening over an extended period, possibly by the reduction of early expression of proinflammatory cytokines. This 7-day treatment minimizes the risk of unwanted side effects of long-term dexamethasone treatment and may be a new approach to prevent graft failure.
Schepers
Abbey
A
Gaubius Laboratory, TNO Quality of Life, Leiden University Medical Center, The Netherlands.
Pires
Nuno M M
NM
Eefting
Daniel
D
de Vries
Margreet R
MR
van Bockel
J Hajo
JH
Quax
Paul H A
PH
D000818:Animals; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D001483:Base Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012501:Saphenous Vein / Q000187:drug effects* / Q000473:pathology; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014656:Vascular Surgical Procedures / Q000009:adverse effects / Q000379:methods
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D012333:RNA, Messenger; C052720:apolipoprotein E3 (Leidein); D003907:Dexamethasone