ABSTRACT
Previous studies in our laboratory have shown that the pleiotropic cytokine leukemia inhibitory factor (LIF) inhibits neointimal formation and the development and progression of atherosclerotic and restenotic lesions in a rabbit model of disease. The present study demonstrates an upregulation of both the LIF receptor (LIFR)-alpha subunit and the signal transducing subunit gp130 following endothelial denudation of the carotid artery by balloon catheter. Continuous infusion of LIF (30 microg/kg/day) resulted in the downregulation of LIFR-alpha in injured arteries in vivo. Similarly, smooth muscle cells in vitro treated with LIF exhibited a time-dependent reduction in LIFR-alpha protein expression and the subsequent reduction in transcription of the TIMP-1 gene. However, in the presence of an intact endothelium, LIFR-alpha was upregulated in response to LIF, and accordingly the downstream induction of iNOS expression was also increased. Thus, LIF exerts more potent antiatherogenic effects in the vasculature when the endothelium is intact.
