Apolipoprotein E mimetic peptide dramatically lowers plasma cholesterol and restores endothelial function in watanabe heritable hyperlipidemic rabbits

Article

关键词: ACUTE CORONARY SYNDROMES;    A AMPHIPATHIC HELIX;    DENSITY-LIPOPROTEIN;    NITRIC-OXIDE;    WHHL-RABBIT;    I-MILANO;    SUPEROXIDE;    ATHEROSCLEROSIS;    METABOLISM;    INFUSION;   

DOI  :  10.1161/CIRCULATIONAHA.104.497107

来源: SCIE

【 摘 要 】

Background - These studies were designed to determine whether the dual-domain peptide with a class A amphipathic helix linked to the receptor-binding domain of apolipoprotein (apo) E (Ac-hE-18A-NH2) possesses both antidyslipidemic and antiinflammatory properties. Methods and Results - A single bolus (15 mg/kg IV) of Ac-hE-18A-NH2 that contains LRKLRKRLLR (141- to 150-residue region of apo E) covalently linked to apo A-I mimetic peptide 18A not only reduced plasma cholesterol levels ( baseline, 562 +/- 29.0 mg/dL versus 287.7 +/- 22.0 mg/dL at 18 hours, P < 0.001) in the Watanabe heritable hyperlipidemic rabbit model but also significantly improved arterial endothelial function. This improvement was associated with a reduction in 2 markers of oxidative stress. First, the plasma lipid hydroperoxide content was reduced significantly, an effect associated with a 5-fold increase in HDL paraoxonase activity. Second, the formation of superoxide anion, a scavenger of nitric oxide, was also significantly reduced in arteries of these animals. Conclusions - Because dyslipidemia and endothelial dysfunction are common features of the atherosclerotic disease process, this unique dual-domain peptide has ideal composite properties that ameliorate key contributory factors to atherosclerosis.

【 授权许可】

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