© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Temporal and spatial distribution of interleukin-1β in balloon injured porcine coronary arteries
Cardiovascular Medicine, Section of Medicine, Division of Clinical Sciences (NGH), University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK
* Corresponding author. Tel: +44-114-271-4004; fax: +44-114-261-9587 j.chamberlain{at}sheffield.ac.uk
Objective: Interleukin-1β (IL-1β) is a proinflammatory cytokine with a wide range of biological activities. We determined the distribution of IL-1β following percutaneous transluminal coronary angioplasty (PTCA) of porcine arteries, and the presence of caspase-1 (required for the activation of IL-1β). Methods: Oversized balloon angioplasty was performed in Yorkshire White pigs and the vessels excised at selected intervals (1, 6, 18 h, 3, 7, and 14 days) post-PTCA. IL-1β and caspase-1 were then identified using reverse transcription polymerase chain reaction (RT-PCR), in situ RT-PCR, and immunohistochemistry. Results: IL-1β protein was detected in the inflammatory infiltrate up to 3 days after PTCA. Luminal endothelial cells contained IL-1β at 1 h, with peak expression at 3–7 days. Adventitial capillaries were IL-1β-positive at all timepoints. IL-1β was detected in adventitial cells at 3 days, with reduced levels at 7 and 14 days. At 7 days, neointimal cells were also IL-1β positive. No IL-1β was detected in non-PTCA control arteries. RT-PCR demonstrated IL-1β mRNA expression to be induced at 1 h, and absent at 3 days. In situ RT-PCR revealed this expression to be distributed throughout the arterial layers at 6 h, but localized to the adventitia at 18 h, with a baseline expression in the adventitial layer of non-PTCA controls. Caspase-1 was detected in luminal endothelial cells from 6 h, in adventitial cells from 3 days, and in neointimal cells from 7 days post-PTCA. This expression colocalized with IL-1β, indicating the potential for the IL-1β present to become activated. Conclusions: We conclude that IL-1β is synthesised, in conjunction with caspase-1, by endothelial, inflammatory, and adventitial cells early (within 3 days) after PTCA, with decreased levels at later timepoints, suggesting that it has a key role to play in the early stages of healing following PTCA.
KEYWORDS IL-1β=interleukin-1β; ICE=interleukin-1 converting enzyme/caspase-1; PTCA=percutaneous transluminal coronary angioplasty; VSMC=vascular smooth muscle cell; IEL=internal elastic lamina; ABC=avidin biotin complex; DAB=3,3'diaminobenzidine tetrahydrochloride; DBA lectin=Dolichos biflorus lectin; 
SMA=-smooth muscle actin; PCNA=proliferating cell nuclear antigen
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