Chronic infusion of salusin-α and -β exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice

ObjectiveHuman salusin-α and -β are two-related peptides processed from the same precursor, preprosalusin. Our previous in vitro studies have shown that human macrophage foam cell formation is stimulated by salusin-β but suppressed by salusin-α. Thus we investigated the effects of salusin-α and -β on atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE−/−) mice.MethodsSaline (vehicle), salusin-α or -β (0.6 nmol/kg/h) was continuously infused through osmotic mini-pumps into 13-week-old ApoE−/− mice for 8 weeks. Aortic atherosclerosis, oxidized LDL-induced cholesterol ester accumulation (foam cell formation), and its related gene expression in exudate peritoneal macrophages were determined.ResultsAfter 4-week infusion of salusin-β, atherosclerotic lesions were 2.6 times greater than vehicle controls, which paralleled 1.9-fold increase in foam cell formation and up-regulation of scavenger receptors (CD36, scavenger receptor class A) and acyl-CoA: cholesterol acyltransferase-1 (ACAT1). In contrast, salusin-α decreased serum total cholesterol levels by 15% and foam cell formation by 68% associated with ACAT1 down-regulation. After 8-week infusion of salusin-α, atherosclerotic lesions were significantly suppressed by 54% compared with vehicle controls.ConclusionsOur study provided the first evidence that salusin-β accelerates the development of atherosclerotic lesions associated with up-regulation of scavenger receptors and ACAT1 in ApoE−/− mice. Whilst, salusin-α exerts anti-atherosclerotic effects by suppressing serum total cholesterol levels and ACAT1 expression.