Regulation of macrophage foam cell formation and atherosclerosis by novel regulatory peptides for cardiovascular system

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Continuous subcutaneous infusion of urotensin II, a strong vasoconstrictor peptide, enhanced atherosclerotic lesions by 8-fold in fat-fed apoE-knockout mice. Analyses of peritoneal macrophages from urotensin II-treated mice revealed 7-fold increase in foam cell formation induced by oxidized LDL. Salusins are novel vasoregulatory peptides that derive from the same precursor. Development of atherosclerosis in apoE-KO mice was suppressed by 68% by continuous subcutaneous infusion of salusin-α but was 2.6-fold enhanced by salusin-β. Peritoneal macrophages from salusin?α-treated mice revealed 68% reduction in foam cell formation induced by oxidized LDL whereas macrophages from salusin-β-treated mice showed 2.6-fold increase in foam cell formation. Thus, urotensin II and salusins can be regarded as novel therapeutic targets for atherosclerosis.