Coronary artery endothelial interleukin-1 beta mediates enhanced fibronectin production related to post-cardiac transplant arteriopathy in piglets.

BACKGROUND

Graft coronary arteriopathy has become the major complication observed in the late follow-up of cardiac transplant patients. We investigated this process experimentally in piglets after a heterotopic cardiac transplant and observed early changes in donor coronary arteries compatible with an immune-inflammatory process, ie, there is increased expression of interleukin-1 beta (IL-1 beta), fibronectin, and activated lymphocytes associated with intimal thickening.

METHODS AND RESULTS

In this study, we cultured porcine coronary artery endothelial cells from host and donor hearts and found similarities in morphology and uptake of acetylated low-density lipoprotein (LDL). As well, host and donor cells showed similar patterns of growth, protein, and glycosaminoglycan synthesis. Endothelial cell fibronectin synthesis was determined after radiolabeling with [35S]-methionine in serum-free medium, gelatin-sepharose extraction of the culture medium and resolution on 5% SDS-PAGE. Donor coronary artery endothelial cell fibronectin synthesis was up to fivefold higher than that of host but was not associated with comparable increased levels of fibronectin mRNA. IL-1 beta appeared to mediate this enhanced fibronectin production, since the IL-1 receptor antagonist caused a 50% decrease in this feature, a change not observed in host cells. Furthermore, donor endothelial cells produced twice the amount of IL-1 beta compared with host cells as judged by immunoprecipitation.

CONCLUSIONS

Increased donor coronary artery endothelial cell fibronectin appears to be regulated at least partly by an autocrine mechanism involving IL-1 beta, and fibronectin may mediate lymphocyte trafficking and smooth muscle cell migration related to graft arteriopathy.