Intermedin ameliorates atherosclerosis in ApoE null mice by modifying lipid profiles

Abstract

Intermedin (IMD) is a recently discovered vasodilator peptide. We studied the role of IMD in the pathogenesis of atherosclerosis by investigating the ability of exogenous IMD to alter lipid profiles and ameliorate the development of atherogenic-diet induced atherosclerosis in ApoE-/- mice. Ten of eight-week-old male C57BL/6J mice were as control. Thirty of eight-week-old male ApoE-/- mice were fed with an atherogenic diet for 18 weeks. After feeding atherogenic diet for 12 weeks, the mice were equally and randomly divided into three groups. Normal saline was given in group A and C57BL/6J mice. Intermedin was given by mini osmotic pumps at the dosage of 100 ng/kg/h and 500 ng/kg/h in group B and group C respectively. After the treatment of IMD for 6 weeks, aortic ultrasonography of group C showed that IMD prevented the progression of atherosclerotic lesions and the increase of wall thickness in the aorta. Oil-red-O staining of the entire aorta and the atherosclerotic aortic root section showed 2 folds decrease atherogenic plaque (p<0.05). Serum lipid profiles were measured, compared with the group A, in group C TC and LDL-C levels were decreased by 86.32% and 89.68%, respectively (both p<0.05), meanwhile, HDL-C level was significantly increased by 74.82% (p<0.05). These data indicate that exogenous administration of IMD could prevent the progression of atherosclerotic plaque. The possible underlying mechanisms may relate to the improvement of lipid profiles.