Turnover of synthetic class A amphipathic peptide analogues of exchangeable apolipoproteins in rats. Correlation with physical properties.

Garber, David W.; Venkatachalapathi, Y. V.; Gupta, Kiran; Ibdah, Jamal A.; Phillips, Michael C.; Hazelrig, Jane B.; Segrest, Jere P.; Anantharamaiah, G.M.

doi:10.1161/01.atv.12.8.886

Cited by 38 publications

(32 citation statements)

References 28 publications

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“…Most of the radioactivity from both L-18A and D-18A was found in the liver and kidney. Because free 125 I did not appear in plasma or urine after injection of D-18A (in contrast to the case after injection of L-18A), it was concluded that D-18A remained in the tissues undegraded 3 days after injection (39). Thus, it is likely that in the case of peptides synthesized from all D-amino acids, some nondegraded peptide will remain in tissues for an undetermined prolonged period.…”

Section: Discussionmentioning

confidence: 98%

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Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits

Lenten

Wagner

Navab

et al. 2007

Journal of Lipid Research

103

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Rabbits on a 1% cholesterol diet received injections of vehicle with or without D-4F or L-4F. After 1 month, the percent of aorta with atherosclerotic lesions was 24 6 15% (vehicle), 10 6 6% (D-4F) (P , 0.01 vs. vehicle), and 13 6 9% (L-4F) (P , 0.05 vs. vehicle). Inflammatory indexes for HDL and LDL were determined by measuring monocyte chemotactic activity after adding rabbit lipoproteins to human endothelial cells. HDL-inflammatory index (HII) and LDL-inflammatory index (LII), respectively, were 1.39 6 0.24; 1.35 6 0.29 (vehicle), 0.67 6 0.26; 0.63 6 0.38 (D-4F) (P , 0.001 vs. vehicle), and 0.67 6 0.2; 0.68 6 0.32 (L-4F) (P , 0.01 vs. vehicle). Serum amyloid A (SAA) levels were 95 6 39, 8 6 22, and 7 6 19 mg/ml, respectively, for vehicle, D-4F, and L-4F (P , 0.001 vs. vehicle). There was no correlation between lesion area and total plasma or HDL-cholesterol levels. In contrast, there was a positive correlation with HII, LII, and SAA (P 5 0.002, P 5 0.0026, P 5 0.0079, respectively). HII correlated closely with SAA levels (r 5 0.6616; r 2 5 0.4377, P , 0.0001). Thus, HII, LII, and SAA are better predictors of lesion area than are total plasma or HDLcholesterol levels in cholesterol-fed rabbits.-Van Lenten, B. J., A. C. Wagner, M. Navab, G. M. Anantharamaiah, S. Hama, S. T. Reddy, and A. M. Fogelman. Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits. J. Lipid Res.

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Section: Discussionmentioning

confidence: 98%

“…Garber et al (39) reported on the tissue distribution and excretion of the peptide 18A. This peptide differs from 4F in that 18A does not have blocking groups as does 4F, and in 4F, two of the leucines on the hydrophobic face of the peptide have been changed to phenylalanines.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits

Lenten

Wagner

Navab

et al. 2007

Journal of Lipid Research

103

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“…In some mice in the D4F IP group, the blood was collected 1 hour after D4F injection to determine D4F concentration by reverse-phase high-performance liquid chromatography as described previously. 25 Serum was stored at Ϫ80°C until analysis. Total cholesterol levels were measured with a commercially available kit (Sigma).…”

Section: Plasma Collection and Analytical Methodsmentioning

confidence: 99%

Differential Effects of Apolipoprotein A-I–Mimetic Peptide on Evolving and Established Atherosclerosis in Apolipoprotein E-Null Mice

et al. 2004

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Background-Apolipoprotein (apo) A-I and apoA-I-mimetic peptides showed promise to prevent atherosclerosis development. Using a bypassed vein graft model in apoE-null mice, we evaluated the effects of oral or intraperitoneal administration of an apoA-I-mimetic peptide on evolving atherosclerotic lesions in the vein graft and compared such effects on the established atherosclerotic lesions in aortic sinus in the same mice. Methods and Results-We used apoE-null mice in which a segment of inferior vena cava was grafted into the right carotid artery at 16 weeks of age. Native aortic atherosclerotic lesions (established atherosclerosis) and vein-graft atherosclerotic lesions (evolving atherosclerosis) were assessed 4 weeks after daily oral (0.3 mg/mL) or intraperitoneal (50 g in 200 L saline) administration of an apoA-I-mimetic peptide, D4F. Mice receiving saline or water without D4F served as controls. Both oral and intraperitoneal administration of D4F reduced vein-graft atherosclerotic (evolving lesions) plaque size by 43% and 42%, plaque lipid by 70% and 49%, and macrophage immunoreactivity by 63% and 62%, respectively, compared with controls. In contrast, D4F had no effect on the native aortic sinus atherosclerotic lesions (established lesions). Conclusions-Oral and intraperitoneal administration of the apoA-I-mimetic peptide D4F significantly reduced rapidly evolving atherosclerotic lesions in vein grafts but not established atherosclerotic lesions in aortic sinus. These observations suggest that the type of atherosclerotic lesions and the time of initiation during the course of lesion evolution modulate the beneficial effects of apoA-I-mimetic peptides on atherosclerosis.

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“…Arterial blood samples were collected after 1,5,10,20,30,45,60,120,180, and 240 min. The plasma concentration of 14 C-4F radioactive counts for each time point was measured and expressed as a percentage of counts present in the 1 min sample, as previously described ( 40 ). A similar procedure was used to measure the clearance of LPS from the circulation.…”

Section: C-4f and Bodipy-lps Plasma Clearance Studiesmentioning

confidence: 99%

The apolipoprotein A-I mimetic peptide 4F prevents defects in vascular function in endotoxemic rats

Dai

Datta

Zhang

et al. 2010

Journal of Lipid Research

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Sepsis is a major cause of death in hospitalized patients. Approximately 50% of patients in intensive care units develop sepsis, and the overall mortality rate is 29% ( 1 ). Mortality is due, in large part, to the cytotoxic actions of lipopolysaccharide (LPS), an endotoxic component of the outer membrane of Gram-negative bacteria. LPS is released from bacterial membranes and activates Toll-like receptors (TLR) on monocytes, neutrophils, and other target cells ( 2-5 ). TLRs transduce LPS action by activating nuclear factor (NF)-B-dependent signaling ( 4-6 ). By this mechanism, LPS stimulates the synthesis/release of infl ammatory cytokines, which play an important role in the innate immune response ( 7,8 ). Dysregulation of this infl ammatory response can lead to intravascular coagulation and multiple organ failure. LPS-induced cytokine production also increases expression of nitric oxide synthase 2 (NOS2) and cyclooxygenase 2 (COX-2), thus enhancing the synthesis of nitric oxide (NO) and arachidonic acidderived vasoactive prostanoids. These products have been implicated in hemodynamic disturbances in sepsis by reducing peripheral vascular resistance ( 9-14 ). Cardiovascular (CV) failure, characterized by severe hypotension and cardiac dysfunction, is linked to increased mortality in patients with severe sepsis ( 15-17 ).Lipoproteins are thought to play a role in the neutralization/detoxifi cation of endotoxin (18)(19)(20). Low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) bind to LPS and direct it to the liver for metabolism and excretion (18)(19)(20). HDL is most effective in clearing endotoxin, a property attributed to its relatively high phospholipid content compared with LDL and VLDL ( 18,21 ). With increasing Abstract High density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) reduce infl ammatory responses to lipopolysaccharide (LPS). We tested the hypothesis that the apoA-I mimetic peptide 4F prevents LPS-induced defects in blood pressure and vascular reactivity. Systolic blood pressure (SBP) was measured in rats at baseline and 6 h after injection of LPS (10 mg/kg) or saline vehicle. Subgroups of LPStreated rats also received 4F (10 mg/kg) or scrambled 4F (Sc-4F). LPS administration reduced SBP by 35% compared with baseline. 4F attenuated the reduction in SBP in LPStreated rats (17% reduction), while Sc-4F was without effect. Ex vivo studies showed a reduced contractile response to phenylephrine (PE) in aortae of LPS-treated rats (ED 50 = 459 ± 83 nM) compared with controls (ED 50 = 57 ± 6 nM). This was associated with nitric oxide synthase 2 (NOS2) upregulation. 4F administration improved vascular contractility (ED 50 = 60 ± 9 nM), reduced aortic NOS2 protein, normalized plasma levels of NO metabolites, and reduced mortality in LPS-treated rats. These changes were associated with a reduction in plasma endotoxin activity. In vivo administration of , , GM-082952 (C.R.W. and G.D.) and HL-85282 (H.G.) Abbreviations: apoA-I, apolipoprotein A-I; COX-2,...

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Turnover of synthetic class A amphipathic peptide analogues of exchangeable apolipoproteins in rats. Correlation with physical properties.

Cited by 38 publications

References 28 publications

Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits

Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits

Differential Effects of Apolipoprotein A-I–Mimetic Peptide on Evolving and Established Atherosclerosis in Apolipoprotein E-Null Mice

The apolipoprotein A-I mimetic peptide 4F prevents defects in vascular function in endotoxemic rats

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