Bielicki et al. developed ATI-5261, a peptide consisting of 36 amino acids forming a single amphipathic helix with high aqueous solubility that induced ABCA1mediated cholesterol efflux with similar efficiency as apoA-I (Bielicki et al. 2010). LDL-R knockout mice received a high-fat Western diet for 13 weeks while concomitantly receiving daily intraperitoneal injections of ATI-5261 during the last 6 weeks. In another model, ApoE knockout mice received a Western diet for 18 weeks, followed by a chow diet with concomitant intraperitoneal injections of ATI-5261 every other day for another 6 weeks. The aortic lesion area and plaque lipid content were significantly reduced in mice treated ATI-5261 compared to mice receiving placebo. The decrease in atherosclerosis was accompanied by increased fecal sterol excretion, which is indicative of increased RCT upon ATI-5261 treatment.


ETC-642 is a complex of a 22-amino acid peptide that forms an amphipathic helix and phospholipids. The complex has been shown to exert multiple favorable effects on LDL and HDL particles (Di Bartolo et al. 2011b). Following 12 weeks of treatment in rabbits, a shift in LDL subfractions toward less negatively charged particles was observed, indicating a reduction in proinflammatory oxidized LDL. Moreover, a reduction in the particularly atherogenic small dense LDL (sdLDL) subfraction was noticed. Shortly after infusion of ETC-642, there was also a shift in HDL subfractions toward the antiatherogenic pre-β fraction. Moreover, ETC-642 was shown to be a potent inducer of cholesterol efflux from human macrophages in in vitro assays. It has also been shown in vivo to increase the cholesterol content in the HDL fraction, which may indicate increased reverse cholesterol transport (Di Bartolo et al. 2011a; Iwata et al. 2011). The anti-inflammatory effects of ETC-642 have been demonstrated in rabbit models of acute and chronic inflammation (Di Bartolo et al. 2011a, b). ETC-642 reduced endothelial adhesion molecule expression both in collared carotid arteries and in the aorta of cholesterol-fed rabbits, and this reduction was similar to effect observed in animals treated with reconstituted HDL. ETC-642 has been shown to induce an anti-inflammatory effect, as HDL isolated from ETC-642-treated rabbits decreased TNF-α-induced expression of NF-kB and endothelial adhesion molecules in human coronary artery endothelial cells (HCAECs) (Di Bartolo et al. 2011b). In addition, ETC-642 inhibited TNF-α-induced monocyte adhesion in HCAECs (Di Bartolo et al. 2011a). The efficiency of ETC-642 as an anti-atherosclerotic agent has been demonstrated using intravascular ultrasound (IVUS) in hyperlipidemic rabbits that were treated with either low or high dose (15 or 50 mg/kg, respectively) or placebo two times per week for 12 weeks. Treatment with high-dose ETC-642

significantly inhibited plaque formation compared to controls (Iwata et al. 2011).

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