Leukotriene B4 production in human atherosclerotic plaques.
We evaluated the hypothesis that leukotriene (LT) B4, a potent chemotactic and endothelium-permeabilizing autacoid, may be a factor in the progression of the atherosclerotic lesion. Human vascular fragments, freshly obtained at vascular surgery from saphenous veins, atrial appendages, normal aortas and atherosclerotic lesions (histologically classified as fibrous plaques, fatty plaques and complicated lesions) were incubated at 37 degree C with mechanical agitation, for various times ranging between 5 and 60 minutes, sequentially, with buffer (basal), ionophore A23187 (IONO), and arachidonic acid (AA). After each step medium was assayed for LTB4 production by radioimmunoassay. Incubations were also performed in a chamber allowing selective exposure of the endothelial surface to the medium. Basal production (15 minute incubation, ng/g, mean +/- SD) was lowest for fibrous plaques (0.9 +/- 0.2, n = 38) and saphenous veins (1.0 +/- 0.3, n = 32) and much higher (P less than 0.01) for fatty plaques (7.3 +/- 2.2, n = 35) and complicated lesions (5.3 +/- 3.0, n = 28). A virtual abolition of production was observed after boiling of the vascular fragment. Production was increased in the presence of AA and IONO (in atheromas: 11.5 +/- 4.2 AND 14.3 +/- 5.3, respectively, with 15 minutes incubation), and decreased after incubation with 5-lipooxigenase inhibitors. Peak of ionophore or arachidonic acid-stimulated production in kinetic studies was reached at 20 minutes. LTB4 production was able to reach the luminal surface in both basal and stimulated conditions. There was no relationship with concomitantly measured prostacyclin production (mainly endothelial), while a correlation was found between LTB4 levels and degree of white cell infiltration in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
De Caterina
R
R
C.N.R. Institute of Clinical Physiology, Pisa, Italy.
Mazzone
A
A
Giannessi
D
D
Sicari
R
R
Pelosi
W
W
Lazzerini
G
G
Azzara'
A
A
Forder
R
R
Carey
F
F
Caruso
D
D
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D014680:Veins / Q000378:metabolism
D001095:Arachidonic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin