Diseased vein grafts express elevated inflammatory cytokine levels compared with atherosclerotic coronary arteries.
BACKGROUND
The pathologic modifications characterizing vein graft disease resemble those observed in native arteriosclerosis, but in accelerated form. Although both disorders are considered to be inflammatory diseases, it remains to be determined whether diseased vein grafts and atherosclerotic coronary arteries differentially express inflammatory mediators. Therefore, we examined whether differences in the expression of proinflammatory cytokines by these two distinct vascular pathologies favor the accelerated inflammation within diseased vein grafts.


METHODS
The messengerRNA expression of various cytokines (interleukin-1 beta [IL-1 beta], IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma]) was quantified using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in tissue samples of native saphenous veins (NSV, n = 5), diseased coronary arteries (CAD, n = 25), and diseased vein grafts (VG, n = 13).


RESULTS
Native saphenous veins did not contain any detectable transcripts except for IFN-gamma. As expected, CAD was characterized by the expression of IL-1 beta, IL-6, IL-8, IFN-gamma, and TNF-alpha mRNA. Interestingly VG also expressed these mediators, but at markedly higher levels. Quantification by RT-PCR revealed that, compared with specimens from the CAD group, VG specimens contained 5.8 +/- 1.2 times, 286 +/- 22 times, and 29 +/- 7.3 times as many transcripts for the cytokines IL-1 beta, IL-6 and TNF-alpha, respectively, as well as 25 +/- 8.3 times more transcripts for the chemokine IL-8. In contrast, the expression of IFN-gamma transcripts did not differ among the groups.


CONCLUSIONS
The elevated expression of proinflammatory cytokine transcripts supports the hypothesis that diseased vein grafts, compared with atherosclerotic coronary arteries, are characterized by enhanced inflammatory activity that might accelerate atherosclerotic modifications. This may implicate new therapeutic strategies for the prevention of vein graft disease.
Christiansen
Jan Felix
JF
Department of Cardiac Surgery, Institute for Immunology and Transfusion Medicine, University Hospital, Luebeck, Germany. janfelixchristiansed@gmx.de
Hartwig
Dirk
D
Bechtel
J F Matthias
JF
Klüter
Harald
H
Sievers
Hans- H
H
Schönbeck
Uwe
U
Bartels
Claus
C
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000601:surgery; D023903:Coronary Restenosis / Q000601:surgery; D003331:Coronary Vessels / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis*; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012086:Reoperation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012501:Saphenous Vein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014680:Veins / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein