Aspirin-independent antithrombotic effects of acutely attached cultured endothelial cells on endarterectomized arteries.
We have compared the acute antithrombotic effects of aspirin-treated versus normal endothelial cell (EC) coverage of endarterectomized baboon aortic segments (EAS) incorporated into chronic exteriorized arteriovenous shunts in baboons. Human ECs grown in culture were incubated in control medium or medium containing aspirin (100 mumols/ml) and then attached at saturation density by incubating EC suspensions (6 x 10(5) cells/100 microliters) within EAS for 20 minutes. Nonendarterectomized aortic segments and untreated EAS served as negative and positive controls, respectively. The inhibitory effect of aspirin treatment on EC production of prostacyclin was confirmed by radioimmunoassay of its stable metabolic breakdown product, 6-keto-prostaglandin F1 alpha in supernatant medium. Thrombus formation in vivo was measured as the accumulation of indium 111-labeled platelets on endarterectomy sites in real time by scintillation camera imaging. 111In-labeled platelets were deposited rapidly, reaching a plateau by 60 minutes of 4.40 +/- 0.89 x 10(9) platelets/cm, compared with 111In-labled platelet deposition on nonendarterectomized segments of 0.89 +/- 0.26 x 10(9) platelets/cm (p = 0.008). Coverage of EAS with normal cultured ECs significantly reduced platelet deposition on EAS (1.05 +/- 0.45 x 10(9) platelets/cm; p = 0.009 at 1 hour compared with EAS not incubated with ECs). Aspirin-treated ECs also produced a marked reduction in platelet disposition (0.71 +/- 0.24 x 10 platelets/cm; p = 0.007 compared with EAS without ECs) that was equivalent to the effect of non-aspirin-treated ECs (p greater than 0.5). Scanning and transmission electron microscopy confirmed the antithrombotic effects of attached ECs. We conclude that endarterectomy of normal arteries produces a highly thrombogenic surface and the thrombogenicity is abolished by acutely attaching cultured human ECs.
Krupski
W C
WC
Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Bass
A
A
Anderson
J S
JS
Kelly
A B
AB
Harker
L A
LA
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004691:Endarterectomy; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010976:Platelet Count; D012016:Reference Values; D013927:Thrombosis / Q000517:prevention & control*
D001241:Aspirin