Apolipoprotein E (apoE) is a ligand for clearance of lipoprotein remnants such as chylomicrons and very low-density lipoproteins. It has anti-atherogenic and anti-inflammatory properties. Therefore, there is extensive ongoing research to create peptides that can mimic properties of apoE. A number of synthetic peptides that encompass different regions of apoE have been studied for inhibiting inflammatory states, including Alzheimer disease. However, peptides that clear atherogenic lipoproteins, analogous to apoE, via enhanced hepatic uptake have not been previously reviewed. Toward this end, we describe the design and studies of a dual-domain apoE mimetic peptide, Ac-hE18A-NH2. This peptide consists of residues 141–150, the putative receptor-binding region of human apoE, covalently linked to a well characterized class A amphipathic helix, 18A, which has no sequence homology to any other exchangeable apolipoprotein sequences. It demonstrates dramatic effects in reducing plasma cholesterol levels in dyslipidemic mouse and rabbit models. We discuss the scientific rationale and review the literature for the design and efficacy of the peptide. Analogous to apoE, this peptide bypasses the low-density lipoprotein receptor for the hepatic uptake of atherogenic lipoproteins via heparan sulfate proteoglycan (HSPG). ApoE mimetics such as Ac-hE18A-NH2 may therefore restore or replace ligands in genetically induced hyperlipidemias to enable reduction in atherogenic lipoproteins via HSPG even in the absence of functional low-density lipoprotein receptors. Therefore, this and similar peptides may be useful in the treatment of dyslipidemic disorders such as familial hyperlipidemia and atherosclerosis.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Eriksson M, Carlson LA, Miettinen TA, et al. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I: potential reverse cholesterol transport in humans. Circulation 1999 Aug 10; 100(6): 594–8.
Newton RS, Krause BR. HDL therapy for the acute treatment of atherosclerosis. Atheroscler Suppl 2002 Dec; 3(4): 31–8.
Chiesa G, Monteggia E, Marchesi M, et al. Recombinant apolipoprotein A-I(Milano) infusion into rabbit carotid artery rapidly removes lipid from fatty streaks. Circ Res 2002 May 17; 90(9): 974–80.
Zhang Y, Zanotti I, Reilly MP, et al. Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivo. Circulation 2003 Aug 12; 108(6): 661–3.
Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003 Nov 5; 290(17): 2292–300.
Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988 Jan–Feb; 8(1): 1–21.
Linton MF, Atkinson JB, Fazio S. Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation. Science 1995 Feb 17; 267(5200): 1034–7.
Davignon J, Cohn JS, Mabile L, et al. Apolipoprotein E and atherosclerosis: insight from animal and human studies. Clin Chim Acta 1999 Aug; 286(1–2): 115–43.
Davignon J. Apolipoprotein E and atherosclerosis: beyond lipid effect. Arterioscler Thromb Vasc Biol 2005 Feb; 25(2): 267–9.
Van Lenten BJ, Wagner AC, Anantharamaiah GM, et al. Apolipoprotein A-I mimetic peptides. Curr Atheroscler Rep 2009 Jan; 11(1): 52–7.
Mahley RW, Weisgraber KH, Hussain MM, et al. Intravenous infusion of apolipoprotein E accelerates clearance of plasma lipoproteins in rabbits. J Clin Invest 1989 Jun; 83(6): 2125–30.
Shimano H, Yamada N, Katsuki M, et al. Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B. J Clin Invest 1992 Nov; 90(5): 2084–91.
Zhang SH, Reddick RL, Piedrahita JA, et al. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 1992 Oct 16; 258(5081): 468–71.
Wetterau JR, Aggerbeck LP, Rall Jr SC, et al. Human apolipoprotein E3 in aqueous solution: I. Evidence for two structural domains. J Biol Chem 1988 May 5; 263(13): 6240–8.
Aggerbeck LP, Wetterau JR, Weisgraber KH, et al. Human apolipoprotein E3 in aqueous solution: II. Properties of the amino- and carboxyl-terminal domains. J Biol Chem 1988 May 5; 263(13): 6249–58.
Cardin AD, Hirose N, Blankenship DT, et al. Binding of a high reactive heparin to human apolipoprotein E: identification of two heparin-binding domains. Biochem Biophys Res Commun 1986 Jan 29; 134(2): 783–9.
Bocksch L, Stephens T, Lucas A, et al. Apolipoprotein E: possible therapeutic target for atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord 2001 Dec; 1(2): 93–106.
Mahley RW, Ji ZS. Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E. J Lipid Res 1999 Jan; 40(1): 1–16.
Herz J, Chen Y, Masiulis I, et al. Expanding functions of lipoprotein receptors. J Lipid Res 2009 Apr; 50 Suppl.: S287–92.
Hatters DM, Peters-Libeu CA, Weisgraber KH. Apolipoprotein E structure: insights into function. Trends Biochem Sci 2006 Aug; 31(8): 445–54.
Bradley WA, Hwang SL, Karlin JB, et al. Low-density lipoprotein receptor binding determinants switch from apolipoprotein E to apolipoprotein B during conversion of hypertriglyceridemic very-low-density lipoprotein to low-density lipoproteins. J Biol Chem 1984 Dec 10; 259(23): 14728–35.
Innerarity TL, Mahley RW. Enhanced binding by cultured human fibroblasts of apo-E-containing lipoproteins as compared with low density lipoproteins. Biochemistry 1978 Apr 18; 17(8): 1440–7.
Yamada N, Shimano H, Mokuno H, et al. Increased clearance of plasma cholesterol after injection of apolipoprotein E into Watanabe heritable hyperlipidemic rabbits. Proc Natl Acad Sci U S A 1989 Jan; 86(2): 665–9.
Mahley RW, Rall Jr SC. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000; 1: 507–37.
Matsuura F, Wang N, Chen W, et al. HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway. J Clin Invest 2006 May; 116(5): 1435–42.
Mahley RW, Huang Y, Weisgraber KH. Putting cholesterol in its place: apoE and reverse cholesterol transport. J Clin Invest 2006 May; 116(5): 1226–9.
Ishigami M, Swertfeger DK, Granholm NA, et al. Apolipoprotein E inhibits platelet-derived growth factor-induced vascular smooth muscle cell migration and proliferation by suppressing signal transduction and preventing cell entry to G1 phase. J Biol Chem 1998 Aug 7; 273(32): 20156–61.
Kelly ME, Clay MA, Mistry MJ, et al. Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin 2 with reduced biological activity. Cell Immunol 1994 Dec; 159(2): 124–39.
Vogel T, Guo NH, Guy R, et al. Apolipoprotein E: a potent inhibitor of endothelial and tumor cell proliferation. J Cell Biochem 1994 Mar; 54(3): 299–308.
Stannard AK, Riddell DR, Sacre SM, et al. Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J Biol Chem 2001 Dec 7; 276(49): 46011–6.
Mullick AE, Powers AF, Kota RS, et al. Apolipoprotein E3- and nitric oxide-dependent modulation of endothelial cell inflammatory responses. Arterioscler Thromb Vasc Biol 2007 Feb; 27(2): 339–45.
Weisgraber KH. Apolipoprotein E: structure-function relationships. Adv Protein Chem 1994; 45: 249–302.
Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci U S A 2006 Apr 11; 103(15): 5644–51.
Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer’s disease to AIDS. J Lipid Res 2009 Apr; 50 Suppl.: S183–8.
Sparrow JT, Sparrow DA, Culwell AR, et al. Apolipoprotein E: phospholipid binding studies with synthetic peptides containing the putative receptor binding region. Biochemistry 1985 Nov 19; 24(24): 6984–8.
Dyer CA, Curtiss LK. A synthetic peptide mimic of plasma apolipoprotein E that binds the LDL receptor. J Biol Chem 1991 Dec 5; 266(34): 22803–6.
Sparrow JT, Sparrow DA, Fernando G, et al. Apolipoprotein E: phospholipid binding studies with synthetic peptides from the carboxyl terminus. Biochemistry 1992 Feb 4; 31(4): 1065–8.
Maulik PR, Reed RA, Sparrow DA, et al. Crystallization and preliminary x-ray diffraction study of synthetic apolipoprotein E fragment (residues 129–169). J Biol Chem 1990 Jan 5; 265(1): 490–2.
Taylor JW, Shih IL, Lees AM, et al. Surface-induced conformational switching in amphiphilic peptide segments of apolipoproteins B and E and model peptides. Int J Pept Protein Res 1993 Jun; 41(6): 536–47.
Dyer CA, Cistola DP, Parry GC, et al. Structural features of synthetic peptides of apolipoprotein E that bind the LDL receptor. J Lipid Res 1995 Jan; 36(1): 80–8.
Wang G, Pierens GK, Treleaven WD, et al. Conformations of human apolipoprotein E(263–286) and E(267–289) in aqueous solutions of sodium dodecyl sulfate by CD and 1H NMR. Biochemistry 1996 Aug 13; 35(32): 10358–66.
Clayton D, Brereton IM, Kroon PA, et al. NMR studies of the low-density lipoprotein receptor-binding peptide of apolipoprotein E bound to dodecylphosphocholine micelles. Protein Sci 1999 Sep; 8(9): 1797–805.
Raussens V, Mah MK, Kay CM, et al. Structural characterization of a low density lipoprotein receptor-active apolipoprotein E peptide, ApoE3-(126–183). J Biol Chem 2000 Dec 8; 275(49): 38329–36.
Raussens V, Slupsky CM, Ryan RO, et al. NMR structure and dynamics of a receptor-active apolipoprotein E peptide. J Biol Chem 2002 Aug 9; 277(32): 29172–80.
Raussens V, Slupsky CM, Sykes BD, et al. Lipid-bound structure of an apolipoprotein E-derived peptide. J Biol Chem 2003 Jul 11; 278(28): 25998–6006.
Dyer CA, Smith RS, Curtiss LK. Only multimers of a synthetic peptide of human apolipoprotein E are biologically active. J Biol Chem 1991 Aug 15; 266(23): 15009–15.
Clay MA, Anantharamaiah GM, Mistry MJ, et al. Localization of a domain in apolipoprotein E with both cytostatic and cytotoxic activity. Biochemistry 1995 Sep 5; 34(35): 11142–51.
Crutcher KA, Clay MA, Scott SA, et al. Neurite degeneration elicited by apolipoprotein E peptides. Exp Neurol 1994 Nov; 130(1): 120–6.
Tolar M, Marques MA, Harmony JA, et al. Neurotoxicity of the 22kDa thrombin-cleavage fragment of apolipoprotein E and related synthetic peptides is receptor-mediated. J Neurosci 1997 Aug 1; 17(15): 5678–86.
Wang XS, Gruenstein E. Rapid elevation of neuronal cytoplasmic calcium by apolipoprotein E peptide. J Cell Physiol 1997 Oct; 173(1): 73–83.
Nikoulin IR, Curtiss LK. An apolipoprotein E synthetic peptide targets to lipoproteins in plasma and mediates both cellular lipoprotein interactions in vitro and acute clearance of cholesterol-rich lipoproteins in vivo. J Clin Invest 1998 Jan 1; 101(1): 223–34.
Wang X, Ciraolo G, Morris R, et al. Identification of a neuronal endocytic pathway activated by an apolipoprotein E (apoE) receptor binding peptide. Brain Res 1997 Dec 5; 778(1): 6–15.
Wang X, Luebbe P, Gruenstein E, et al. Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways. J Neurosci Res 1998 Mar 1; 51(5): 658–65.
Mousazadeh M, Palizban A, Salehi R, et al. Gene delivery to brain cells with apoprotein E derived peptide conjugated to polylysine (apoEdp-PLL). J Drug Target 2007 Apr; 15(3): 226–30.
Moulder KL, Narita M, Chang LK, et al. Analysis of a novel mechanism of neuronal toxicity produced by an apolipoprotein E-derived peptide. J Neurochem 1999 Mar; 72(3): 1069–80.
Zhang G, Curtiss LK, Wade RL, et al. An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17alpha-hydroxylase, C17–20 lyase. J Lipid Res 1998 Dec; 39(12): 2406–14.
Zerbinatti CV, Dyer CA. Apolipoprotein E peptide stimulation of rat ovarian theca cell androgen synthesis is mediated by members of the low density lipoprotein receptor superfamily. Biol Reprod 1999 Sep; 61(3): 665–72.
Sauer I, Dunay IR, Weisgraber K, et al. An apolipoprotein E-derived peptide mediates uptake of sterically stabilized liposomes into brain capillary endothelial cells. Biochemistry 2005 Feb 15; 44(6): 2021–9.
Pham T, Kodvawala A, Hui DY. The receptor binding domain of apolipoprotein E is responsible for its antioxidant activity. Biochemistry 2005 May 24; 44(20): 7577–82.
Kelly BA, Neil SJ, McKnight A, et al. Apolipoprotein E-derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity. FEBS J 2007 Sep; 274(17): 4511–25.
Bhattacharjee PS, Neumann DM, Foster TP, et al. Effective treatment of ocular HSK with a human apolipoprotein E mimetic peptide in a mouse eye model. Invest Ophthalmol Vis Sci 2008 Oct; 49(10): 4263–8.
Bhattacharjee PS, Neumann DM, Hill JM. A human apolipoprotein E mimetic peptide effectively inhibits HSV-1 TK-positive and TK-negative acute epithelial keratitis in rabbits. Curr Eye Res 2009 Feb; 34(2): 99–102.
Minami SS, Cordova A, Cirrito JR, et al. ApoE mimetic peptide decreases Abeta production in vitro and in vivo. Mol Neurodegener 2010; 5: 16.
Bhattacharjee PS, Huq TS, Mandal TK, et al. A novel peptide derived from human apolipoprotein E is an inhibitor of tumor growth and ocular angiogenesis. PLoS One 2011; 6(1): e15905.
Gao J, Wang H, Sheng H, et al. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care 2006; 4(1): 25–31.
Li FQ, Sempowski GD, McKenna SE, et al. Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in a murine model of multiple sclerosis. J Pharmacol Exp Ther 2006 Sep; 318(3): 956–65.
Wang H, Durham L, Dawson H, et al. An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer’s disease pathology following closed head injury: evidence of pharmacogenomic interaction. Neuroscience 2007 Feb 23; 144(4): 1324–33.
Laskowitz DT, McKenna SE, Song P, et al. COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. J Neurotrauma 2007 Jul; 24(7): 1093–107.
Hoane MR, Pierce JL, Holland MA, et al. The novel apolipoprotein E-based peptide COG1410 improves sensorimotor performance and reduces injury magnitude following cortical contusion injury. J Neurotrauma 2007 Jul; 24(7): 1108–18.
Singh K, Chaturvedi R, Asim M, et al. The apolipoprotein E-mimetic peptide COG112 inhibits the inflammatory response to Citrobacter rodentium in colonic epithelial cells by preventing NF-kappaB activation. J Biol Chem 2008 Jun 13; 283(24): 16752–61.
Li FQ, Fowler KA, Neil JE, et al. An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury. J Pharmacol Exp Ther 2010 Jul; 334(1): 106–15.
Kaufman NA, Beare JE, Tan AA, et al. COG 1410, an apolipoprotein E-based peptide, improves cognitive performance and reduces cortical loss following moderate fluid percussion injury in the rat. Behav Brain Res 2010 Dec 25; 214(2): 395–401.
Laskowitz DT, Thekdi AD, Thekdi SD, et al. Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides. Exp Neurol 2001 Jan; 167(1): 74–85.
Singh K, Chaturvedi R, Barry DP, et al. The apolipoprotein E-mimetic peptide COG112 inhibits NF-kappaB signaling, proinflammatory cytokine expression, and disease activity in murine models of colitis. J Biol Chem 2011 Feb 4; 286(5): 3839–50.
Sheng Z, Prorok M, Brown BE, et al. N-methyl-D-aspartate receptor inhibition by an apolipoprotein E-derived peptide relies on low-density lipoprotein receptor-associated protein. Neuropharmacology 2008 Aug; 55(2): 204–14.
Christensen DJ, Ohkubo N, Oddo J, et al. Apolipoprotein E and peptide mimetics modulate inflammation by binding the SET protein and activating protein phosphatase 2A. J Immunol 2011 Feb 15; 186(4): 2535–42.
Gay EA, Klein RC, Yakel JL. Apolipoprotein E-derived peptides block alpha7 neuronal nicotinic acetylcholine receptors expressed in xenopus oocytes. J Pharmacol Exp Ther 2006 Feb; 316(2): 835–42.
Klein RC, Yakel JL. Inhibition of nicotinic acetylcholine receptors by apolipoprotein E-derived peptides in rat hippocampal slices. Neuroscience 2004; 127(3): 563–7.
McAdoo JD, Warner DS, Goldberg RN, et al. Intrathecal administration of a novel apoE-derived therapeutic peptide improves outcome following perinatal hypoxic-ischemic injury. Neurosci Lett 2005 Jun 24; 381(3): 305–8.
Azuma M, Kojimab T, Yokoyama I, et al. A synthetic peptide of human apoprotein E with antibacterial activity. Peptides 2000 Mar; 21(3): 327–30.
Luo P, Braddock DT, Subramanian RM, et al. Structural and thermodynamic characterization of a bioactive peptide model of apolipoprotein E: side-chain lactam bridges to constrain the conformation. Biochemistry 1994 Oct 18; 33(41): 12367–77.
Braddock DT, Mercurius KO, Subramanian RM, et al. Conformationally specific enhancement of receptor-mediated LDL binding and internalization by peptide models of a conserved anionic N-terminal domain of human apolipoprotein E. Biochemistry 1996 Nov 5; 35(44): 13975–84.
Chang S, ran Ma T, Miranda RD, et al. Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity. Proc Natl Acad Sci U S A 2005 Dec 20; 102(51): 18694–9.
Sauer I, Nikolenko H, Keller S, et al. Dipalmitoylation of a cellular uptake-mediating apolipoprotein E-derived peptide as a promising modification for stable anchorage in liposomal drug carriers. Biochim Biophys Acta 2006 Apr; 1758(4): 552–61.
Pande AH, Tripathy RK. Preferential binding of apolipoprotein E derived peptides with oxidized phospholipid. Biochem Biophys Res Commun 2009 Feb 27; 380(1): 71–5.
Bielicki JK, Zhang H, Cortez Y, et al. A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice. J Lipid Res 2010 Jun; 51(6): 1496–503.
Anantharamaiah GM. Synthetic peptide analogs of apolipoproteins. Methods Enzymol 1986; 128: 627–47.
Rall Jr SC, Weisgraber KH, Innerarity TL, et al. Structural basis for receptor binding heterogeneity of apolipoprotein E from type III hyperlipoproteinemic subjects. Proc Natl Acad Sci U S A 1982 Aug; 79(15): 4696–700.
Wilson C, Wardell MR, Weisgraber KH, et al. Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E. Science 1991 Jun 28; 252(5014): 1817–22.
Datta G, Chaddha M, Garber DW, et al. The receptor binding domain of apolipoprotein E, linked to a model class A amphipathic helix, enhances internalization and degradation of LDL by fibroblasts. Biochemistry 2000 Jan 11; 39(1): 213–20.
Bocksch L, Rider BJ, Stephens T, et al. C-terminal apolipoprotein E-derived peptide, Ep1.B, displays anti-atherogenic activity. Atherosclerosis 2007 Sep; 194(1): 116–24.
Vedhachalam C, Narayanaswami V, Neto N, et al. The C-terminal lipid-binding domain of apolipoprotein E is a highly efficient mediator of ABCA1-dependent cholesterol efflux that promotes the assembly of high-density lipoproteins. Biochemistry 2007 Mar 13; 46(10): 2583–93.
Anantharamaiah GM, Jones MK, Segrest JP. An atlas of the amphipathic helical domains of human exchangeable plasma apolipoproteins. In: Epand RM, editor. The amphipathic helix. Boca Raton (FL): CRC Press, 1993: 109–42.
Anantharamaiah GM, Datta G, Garber DW. Toward the design of peptide mimics of antiatherogenic apolipoproteins A-I and E. Current Science 2001; 81(1): 53–65.
Datta G, Garber DW, Chung BH, et al. Cationic domain 141–150 of apoE covalently linked to a class A amphipathic helix enhances atherogenic lipoprotein metabolism in vitro and in vivo. J Lipid Res 2001 Jun; 42(6): 959–66.
Ramprasad MP, Anantharamaiah GM, Garber DW, et al. Sustained-delivery of an apolipoprotein E-peptidomimetic using multivesicular liposomes lowers serum cholesterol levels. J Control Release 2002 Feb 19; 79(1–3): 207–18.
Garber DW, Handattu S, Aslan I, et al. Effect of an arginine-rich amphipathic helical peptide on plasma cholesterol in dyslipidemic mice. Atherosclerosis 2003 Jun; 168(2): 229–37.
Nayyar G, Handattu SP, Monroe CE, et al. Two adjacent domains (141–150 and 151–160) of apoE covalently linked to a class A amphipathic helical peptide exhibit opposite atherogenic effects. Atherosclerosis 2010 Dec; 213(2): 449–57.
Oldberg A, Kjellen L, Hook M. Cell-surface heparan sulfate: isolation and characterization of a proteoglycan from rat liver membranes. J Biol Chem 1979 Sep 10; 254(17): 8505–10.
Stow JL, Kjellen L, Unger E, et al. Heparan sulfate proteoglycans are concentrated on the sinusoidal plasmalemmal domain and in intracellular organelles of hepatocytes. J Cell Biol 1985 Mar; 100(3): 975–80.
Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988 Apr 29; 240(4852): 622–30.
Gupta H, White CR, Handattu S, et al. Apolipoprotein E mimetic peptide dramatically lowers plasma cholesterol and restores endothelial function in watanabe heritable hyperlipidemic rabbits. Circulation 2005 Jun 14; 111(23): 3112–8.
Garber DW, Kulkarni KR, Anantharamaiah GM. A sensitive and convenient method for lipoprotein profile analysis of individual mouse plasma samples. J Lipid Res 2000 Jun; 41(6): 1020–6.
Datta G, White CR, Dashti N, et al. Anti-inflammatory and recycling properties of an apolipoprotein mimetic peptide, Ac-hE18A-NH(2). Atherosclerosis 2010 Jan; 208(1): 134–41.
Kolodgie FD, Katocs Jr AS, Largis EE, et al. Hypercholesterolemia in the rabbit induced by feeding graded amounts of low-level cholesterol: methodological considerations regarding individual variability in response to dietary cholesterol and development of lesion type. Arterioscler Thromb Vasc Biol 1996 Dec; 16(12): 1454–64.
Higuchi K, Kitagawa K, Kogishi K, et al. Developmental and age-related changes in apolipoprotein B mRNA editing in mice. J Lipid Res 1992 Dec; 33(12): 1753–64.
Young SG. Recent progress in understanding apolipoprotein B. Circulation 1990 Nov; 82(5): 1574–94.
Chung BH, Palgunachari MN, Mishra VK, et al. Probing structure and function of VLDL by synthetic amphipathic helical peptides. J Lipid Res 1996 May; 37(5): 1099–112.
Handattu SP, Datta G, Epand RM, et al. Oral administration of L-mR18L, a single domain cationic amphipathic helical peptide, inhibits lesion formation in ApoE null mice. J Lipid Res 2010 Dec; 51(12): 3491–9.
This work is supported by the following grants: NIHR01 HL090803 (GMA) and NIH 5K08HL085282 (HG). GMA is a principal in Bruin Pharma and is a stock holder in Lipimetix, which has licensed apoE mimetic technology from UAB Research Foundation. DWG and HG have intellectual property rights to certain cationic peptides. DG is a founder of Lipimetix, LLC, which has licensed the apoE mimetic technology from University of Alabama, Birmingham Research Foundation.
About this article
Cite this article
Sharifov, O.F., Nayyar, G., Garber, D.W. et al. Apolipoprotein E Mimetics and Cholesterol-Lowering Properties. Am J Cardiovasc Drugs 11, 371–381 (2011). https://doi.org/10.2165/11594190-000000000-00000
- Plasma Cholesterol Level
- Fast Protein Liquid Chromatography
- Atherogenic Lipoprotein
- Amphipathic Helix
- Lipoprotein Remnant