Effect of an arginine-rich amphipathic helical peptide on plasma cholesterol in dyslipidemic mice

Garber, David W.; Handattu, Shaila P.; Aslan, İbrahim; Datta, Geeta; Chaddha, Manjula; Anantharamaiah, G.M.

doi:10.1016/s0021-9150(03)00101-1

Cited by 39 publications

(61 citation statements)

References 20 publications

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“…2A). These clearance data are similar to those reported in previous studies (17,20), where the hE peptide was linked to 18A to form the lipoprotein-clearing peptide hE-18A. Additionally, it has been previously demonstrated that peptides containing the hE sequence traffic to the liver (40).…”

Section: Resultssupporting

confidence: 90%

“…For Hb-B10 to decrease CF-Hb in the plasma in vivo requires that Hb-B10 both bind to and clear CF-Hb from the circulation. To accomplish both functions in vivo, Hb-B10 was coupled to a fragment of ApoE (hE; LRKLRKRLLR, residues 141-150), which has been shown to effectively clear lipoproteins from the circulation when linked to 18A, a well-characterized class A amphipathic helix that binds lipoproteins (13,14,17,20).…”

Section: Resultsmentioning

confidence: 99%

“…Arbitrary fluorescence values were normalized to a standard curve of FAM-labeled hE-Hb-B10 in mouse plasma to obtain micrograms per milliliter of peptide. These values were then fitted to a double exponential equation to determine t1/2 values of hE-Hb-B10 in plasma (Sigma Plot software, Systac Software, San Jose, CA) (17,20).…”

Section: Methodsmentioning

confidence: 99%

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A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia

Hanson

Flewelen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia

Hanson

Flewelen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Candidates for clearance include HSPG and LRP. In another study, we found that pretreatment of apoE Ϫ / Ϫ mice with heparinase, followed by apoE mimetic administration, did not reduce plasma cholesterol ( 134 ). This result strongly supports that Ac-hE18A-NH 2 clears atherogenic lipoproteins via interaction with HSPGs.…”

Section: Anti-atherogenic and Anti-inflammatory Effects Of Ac-he18a-nhsupporting

confidence: 56%

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review

White

Garber

Anantharamaiah

2014

Journal of Lipid Research

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“…On the basis of the idea that apoE possesses the putative receptor binding domain (141-155 region of apoE) at the N-terminus and a lipid binding domain at the C terminus, we designed a dual-domain peptide Ac-hE18A-NH 2 in which residues 141-150 of apoE, LRKLRKRLLR, is covalently bound to the model class A peptide 18A ( 2 ). This peptide is capable of reducing plasma cholesterol via hepatic uptake and has anti-infl ammatory properties (13)(14)(15). However, this peptide has only been shown to be active when intravenously administered.…”

Section: Right-angle Light Scattering Measurementsmentioning

confidence: 99%

Oral administration of L-mR18L, a single domain cationic amphipathic helical peptide, inhibits lesion formation in ApoE null mice

Handattu

Datta

Epand

et al. 2010

Journal of Lipid Research

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Supplementary key words atherosclerosis • metabolism • animals • lipids • cholesterolAs apolipoprotein (apo)A-I possesses tandem repeating class A amphipathic helical motifs, several investigators (including our own laboratory) have developed peptides that possess the class A amphipathic helical motif and have shown that, similar to apoA-I, several of these peptides not only interact with phospholipids to form nascent HDL-like peptide-lipid discoidal complexes but also possess both anti-infl ammatory and cellular cholesterol effl uxing properties ( 1-3 ). Several papers have been published using 4F and D-4F peptides to demonstrate that the peptides inhibit or slow down the onset of several infl ammatory diseases, including atherosclerosis (reviewed in Ref. 4 ). When 4F is synthesized from all D amino acids, the resulting D-4F is orally active and can be administered either in drinking water or mixed with food to inhibit infl ammatory processes ( 5 ). However, not all of the class A peptides are antiinfl ammatory ( 6, 7 ). It has been shown that the clustering of aromatic residues on the nonpolar face of a class A amphipathic helical motif favors its association with oxidized phospholipid ( 6-9 ).An ideal strategy for inhibiting atherosclerosis would not only decrease plasma cholesterol levels but also increase anti-infl ammatory properties. ApoE, the protein Abstract We have shown that Ac-hE18A-NH 2 , a dual-domain cationic apolipoprotein-mimetic peptide, reduces plasma cholesterol levels in dyslipidemic mice. Two singledomain cationic peptides based on the lytic class L peptide 18L were developed to test the hypothesis that a singledomain cationic amphipathic peptide can reduce atherosclerosis in apolipoprotein (apo)E null mice when orally administered. To incorporate anti-infl ammatory properties, aromatic residues were clustered in the nonpolar face similar to peptide 4F, resulting in modifi ed 18L (m18L). To reduce lytic properties, the Lys residues of 18L were replaced with Arg with the resulting peptide called modifi ed R18L (mR18L). Biophysical studies showed that mR18L had stronger interactions with lipids than did m18L. Peptide mR18L was also more effective than m18L in promoting LDL uptake by HepG2 cells. ApoE null mice received normal chow or chow containing m18L or mR18L for six weeks. A signifi cant reduction in plasma cholesterol and aortic sinus lesion area was seen only in the mR18L group. Plasma from mice administered mR18L, unlike those from the control and m18L groups, did not enhance monocyte adhesion to endothelial cells. Thus oral administration of mR18L reduces plasma cholesterol and lesion formation and inhibits monocyte adhesion. -Handattu, S. P., G. Datta, R. M. Epand, R.

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Effect of an arginine-rich amphipathic helical peptide on plasma cholesterol in dyslipidemic mice

Cited by 39 publications

References 20 publications

A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia

A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review

Oral administration of L-mR18L, a single domain cationic amphipathic helical peptide, inhibits lesion formation in ApoE null mice

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