ApoA-I mimetic peptides promote pre-β HDL formation in vivo causing remodeling of HDL and triglyceride accumulation at higher dose

Carballo-Jane, Ester; Chen, Zhu; O’Neill, Edward A.; Wang, Jun; Burton, Charlotte; Chang, Ching H.; Chen, Xun; Eveland, Suzanne S.; Frantz-Wattley, Betsy; Gagen, Karen; Hubbard, Brian K.; Ichetovkin, Marina; Luell, Silvi; Meurer, Roger; Song, Xuelei S.; Strack, Alison M.; Langella, Annunziata; Cianetti, Simona; Rech, Francesca; Capitò, Elena; Bufali, Simone; Veneziano, Maria; Verdirame, Maria; Bonelli, Fabio; Monteagudo, Edith; Pessi, Antonello; Ingenito, Raffaele; Bianchi, Elisabetta

doi:10.1016/j.bmc.2010.09.074

Cited by 29 publications

(36 citation statements)

References 33 publications

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“…The ability of the C-II peptides to promote in vitro the lipolysis of intralipid, a phospholipid emulsion containing triglycerides, was tested and compared with full-length apoC-II and 5A, an apoA-I mimetic peptide that reduces atherosclerosis and inflammation in animal models (Amar et al, 2010;Tabet et al, 2010;Dai et al, 2012) but causes hypertriglyceridemia (Carballo-Jane et al, 2010). Increasing the concentration of C-II-a increased the generation of FFAs in the presence of LPL, with the maximum effect occurring at about 0.22 mmol/l, thus indicating that the peptide is a potent activator of LPL (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…LPL activity was monitored with either intralipid (2.5 mg TGs per well) as the substrate or with serum (1:50 final dilution) in a reaction volume of 50 ml in phosphate-buffered saline (pH 7.4) containing 0.1% (w/v) fatty acid free bovine serum albumin. The activity was monitored by the release of free fatty acids (FFAs), as previously described (Carballo-Jane et al 2010). A total of 0.2 units of LPL purified from bovine milk (Sigma-Aldrich, St. Louis, MO) was added per well.…”

Section: Methodsmentioning

confidence: 99%

“…One possible limitation of apoA-I mimetic peptides as well as full-length apoA-I is that they have been reported to transiently cause hypertriglyceridemia (Nanjee et al, 1996(Nanjee et al, , 1999Shaw et al, 2008;Carballo-Jane et al, 2010;). One proposed explanation for this phenomenon is their ability to displace apolipoprotein C-II (apoC-II), a known activator of lipoprotein lipase (LPL) (Kei et al, 2012), or they may, like apolipoprotein C-III (apoC-III), cause direct inhibition of LPL (Wang et al, 1985;Shachter et al, 1994;Jong et al, 1999;Ooi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

Amar

Sakurai

Sakurai-Ikuta

et al. 2014

J Pharmacol Exp Ther

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Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E-knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 6 6% and 85 6 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

Amar

Sakurai

Sakurai-Ikuta

et al. 2014

J Pharmacol Exp Ther

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“…Serum levels of apoA-IM, lipids, and (apo)lipoproteins in sera before and after administration of MDCO-216 on day 41 As shown in Fig. 5 , the serum level of apoA-IM showed a very similar kinetic profi le after infusion on day 41 compared with day 1.…”

Section: Methodsmentioning

confidence: 84%

Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys

Kempen¹,

Gomaraschi

Bellibas

et al. 2013

Journal of Lipid Research

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“…This includes the use of ApoAI peptide mimetics [16], which have been designed largely on the structural and physical properties thought to confer the ability of ApoAI to induce cholesterol efflux [17,18]. The result has been a series of short amphipathic α-helical peptides with an ability to both induce cellular cholesterol efflux and modulate immune responses, both in vitro and in vivo [11,[19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Low Doses of Innate Defence Regulator Peptide, IDR-1018, Enhances HDL-Mediated Cholesterol Efflux from Smooth Muscle Cells and Macrophages

Chan

Pistolic³

et al. 2016

JNB

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Cardiovascular diseases due to atherosclerosis are the leading cause of death worldwide. In recent years, novel therapeutics designed to enhance high-density lipoprotein (HDL) activity as a treatment for atherosclerosis have been explored. Of particular interest is the use of amphipathic α-helical peptides to mimic the action of the main HDL protein, apolipoprotein (Apo)AI. Immunomodulatory peptides share many physical and functional properties with ApoAI and its mimetics; we therefore hypothesized that they too might be capable of enhancing cholesterol efflux. The aim of this study was to determine whether a potent immunomodulatory peptide, innate defence regulator (IDR)-1018, could promote cholesterol efflux from cells. Here, we report that IDR-1018 induced a dose-dependent increase in ApoAI on the cell surface and ATP-binding cassette transporter A1 (ABCA1) protein levels. Functional assays revealed that low doses of IDR-1018 improved HDL-mediated suppression of intracellular cholesteryl ester accumulation in macrophages and enhanced HDL-mediated cellular cholesterol efflux from smooth muscle cells and macrophages. Based on these results we propose that natural and synthetic immunomodulatory peptides like IDR-1018 represent a large new group of peptides that could be developed for the treatment of atherosclerosis.

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ApoA-I mimetic peptides promote pre-β HDL formation in vivo causing remodeling of HDL and triglyceride accumulation at higher dose

Cited by 29 publications

References 33 publications

A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys

Low Doses of Innate Defence Regulator Peptide, IDR-1018, Enhances HDL-Mediated Cholesterol Efflux from Smooth Muscle Cells and Macrophages

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