A novel urotensin II receptor antagonist, KR-36676, prevents ABCA1 repression via ERK/IL-1β pathway.

Urotensin II (U-II), the most potent vasoconstrictor peptide known to date, is expressed at a high level in vascular smooth muscle cells (VSMC) and endothelial cells, whereas its receptor, urotensin (UT) receptor, is abundant in monocytes and macrophages of atherosclerotic lesions. U-II is highly present in the coronary arteries of the atherosclerotic patients compared to normal subjects. Recently, U-II was shown to down-regulate ATP binding cassette transporter-A1 (ABCA1) expression, which is responsible for reverse cholesterol transport in macrophages of atherosclerotic lesions.