Reduced prostacyclin and increased leukotriene B4 synthesis in porcine venous-arterial grafts.
BACKGROUND
Migration and proliferation of vascular smooth muscle cells in the intima and superimposed atheroma are the main changes underlying late failure of saphenous vein bypass grafts. There is evidence that these events are partly modulated by complex interactions between inhibitors of vascular smooth muscle cell proliferation, such as prostacyclin (PGI2), and mitogens, such as leukotriene B4 (LTB4). Because the relative balance between these eicosanoids may play a role in vein graft failure, the synthesis of PGI2 and LTB4 was measured in porcine saphenous vein-carotid artery grafts 4 weeks after implantation and compared with ungrafted vein and common carotid artery from the same animal.


METHODS
Vessels were cut into 2-mm squares and preincubated in Dulbecco's minimum essential medium for 4 hours at 37 degrees C. Tissues were then further incubated with Dulbecco's minimum essential medium containing a range of concentrations of noradrenaline, arachidonate, and calcium ionophore A23187. Release of PGI2 and LTB4 into the supernatant was then assessed by radioimmunoassay.


RESULTS
In response to all stimulators, PGI2 release was markedly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. The patterns of responses were similar in each vessel type. In contrast, LTB4 release was significantly enhanced in vein grafts compared to ungrafted saphenous veins and carotid arteries.


CONCLUSIONS
These data indicate that there is a down-regulation of cyclooxygenase or PGI2 synthase in porcine vein grafts, which may constitute a further phenotypic change that would augment the hyperplastic process. Local increases in LTB4 synthesis in the vein graft, which indicates an induction of lipoxygenase and LTB4 synthase enzymes (and possibly reflects release from leukocytes which have infiltrated the graft), may contribute to increased intimal proliferation by direct promitogenic effects on smooth muscle cells.
Jeremy
J Y
JY
Bristol Heart Institute, University of Bristol, United Kingdom.
Izzat
M B
MB
Birkett
S D
SD
Knight
D M
DM
Bryan
A J
AJ
Angelini
G D
GD
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002343:Carotid Artery, Internal / Q000378:metabolism* / Q000601:surgery*; D015536:Down-Regulation; D011464:Epoprostenol / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012501:Saphenous Vein / Q000378:metabolism* / Q000637:transplantation*; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D013729:Terpenes; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D019284:Thapsigargin; D012969:Sodium Fluoride; D011464:Epoprostenol; D009638:Norepinephrine