Oxidized phospholipids as a new landmark in atherosclerosis

Itabe, Hiroyuki

doi:10.1016/s0163-7827(98)00009-5

Cited by 93 publications

(62 citation statements)

References 168 publications

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“…There is controversy in the literature regarding the importance of the PAF-AH activity and concentration in the atherosclerotic process [27][28][29][30][31][32][33] . Some studies demonstrate that patients with DM 1 have low levels of PAF-AH, unlike patients with DM 2 27,29 .…”

Section: Discussionmentioning

confidence: 99%

Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

Castro¹,

Neto²,

Gomes³

2007

Arq. Bras. Cardiol.

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SummaryObjective: To evaluate platelet-activating factor acetylhydrolase (PAF-AH) activity and its relationship with clinical and demographic variables, metabolic control, apolipoprotein A and B levels and the susceptibility of low-density lipoprotein (LDL) to in vitro oxidation in patients with type 1 diabetes mellitus (DM 1).Methods: Forty two patients with DM 1 (27 females) and 48 control subjects (16 females) matched for gender, age and body mass index (BMI) were evaluated. The following tests were performed: fast plasma glucose (FG) and postprandial plasma glucose (PPG), lipid profile, uric acid (UA), glycosylated hemoglobin (HbA1c), and low-density lipoprotein (LDL) oxidation rate using colorimetric assay. The PAF-AH activity was analyzed using colorimetric assay (Cayman Chemical).Results: The analysis of PAF-AH activity showed a higher enzyme activity in patients with DM 1 than in control subjects (0.0150 + 0.0051 vs. 0.0116 + 0.0041; p < 0.001). In patients with DM 1, a direct correlation between PAF-AH activity and age and LDL, and an inverse correlation between PAF-AH and HbA1c and high-density lipoprotein (HDL) were found.Conclusion: In the sample studied, PAF-AH showed a higher activity in patients with DM 1, a factor that may be related to the higher risk of developing cardiovascular diseases observed in these patients. Further studies are necessary to evaluate the real participation of this enzyme in the risk of development of atherosclerotic diseases in patients with DM 1.

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Section: Discussionmentioning

confidence: 99%

Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

Castro¹,

Neto²,

Gomes³

2007

Arq. Bras. Cardiol.

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“…The oxidative modification of LDL is associated with many changes in the chemical composition of LDL, including degradation of apolipoprotein B-100, generation of lipid peroxides and oxysterols, and conversion of PC to LysoPC. 31) LysoPC is generated during LDL oxidation through enzymatic hydrolysis of PC by platelet-activating factor acetylhydrolase, an enzyme that is normally associated with LDL. 32) The known biological activities of OxLDL include chemotactic activity for circulating monocytes, 7,33) a cytotoxic effect on endothelial cells, 9) induction in endothelial cells of several factors such as granulocyte macrophage colony-stimulating factor, 34) cell adhesion molecules, 35) platelet-derived growth factor and heparin-binding epidermal growth factorlike protein, 36) induction of platelet-derived growth factor in smooth muscle cells, 37) impairment of endothelium-dependent arterial relaxation, 8,38) and stimulation of platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

Oxidized Low-Density Lipoprotein-Binding Specificity of the Asp-Hemolysin-Related Synthetic Peptides from Aspergillus fumigatus

Kumagai

Tsutsumi

Ogawa

et al. 2006

Biological & Pharmaceutical Bulletin

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Oxidatively modified low-density lipoprotein (OxLDL) is present in atherosclerotic lesions and has been proposed to play an important role in atherogenesis. In the present study, in order to clarify the structure-binding activity relationship of Asp-hemolysin-related peptides to OxLDL, we investigated the interaction between Asphemolysin-related peptides consisting of 4 to 29 amino acid residues and OxLDL. The incubation of OxLDL with each Asp-hemolysin-related peptide resulted in the formation of an Asp-hemolysin/OxLDL complex. In particular, the tetrapeptide, YKDG (P-4), bound to OxLDL and inhibited the OxLDL-induced macrophage proliferation in a dose-dependent manner. Furthermore, we demonstrated that lysophosphatidylcholine (LysoPC) extracted from OxLDL inhibited the binding of P-21 to OxLDL in a dose-dependent manner and synthetic [ 14 C]LysoPC bound to P-21. We propose here that the YKDG region is one of the important sites for the binding of these peptides to OxLDL, and LysoPC as a typical lipid moiety of OxLDL is attributed to the binding of OxLDL to these peptides.

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“…22) LysoPC is generated during LDL oxidation through enzymatic hydrolysis of PC by PAF-AH, an enzyme that is normally associated with LDL.…”

Section: Discussionmentioning

confidence: 99%

A Synthetic Peptide (P-21) Derived from Asp-Hemolysin Inhibits the Induction of Macrophage Proliferation by Oxidized Low-Density Lipoprotein

Kumagai

Ogawa

Tsutsumi

et al. 2005

Biological & Pharmaceutical Bulletin

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Macrophage-derived foam cells play an important role in atherosclerotic lesions. Oxidized low-density lipoprotein (OxLDL) induces macrophage proliferation via the specific uptake of lysophosphatidylcholine (LysoPC) of OxLDL by class A, type I and type II macrophage scavenger receptors. We have previously shown that Asp-hemolysin from Aspergillus fumigatus binds to LysoPC as a typical lipid moiety of OxLDL. This study investigated the effect of the Asp-hemolysin-related peptide (P-21), a synthetic peptide derived from a region of Asp-hemolysin that is rich in positive charges, on macrophage proliferation induced by OxLDL. Mouse peritoneal macrophages were used for proliferation study. OxLDL induced macrophage proliferation in an oxidation time-dependent manner, and P-21 inhibited OxLDL-induced macrophage proliferation in a dose-dependent manner. Furthermore, the binding analysis of P-21 to OxLDL by dissociation-enhanced lanthanide fluorometric immunoassay indicated that P-21 binds to OxLDL. These results indicate that P-21 inhibits the OxLDL-induced macrophage proliferation through binding of P-21 to OxLDL.

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Oxidized phospholipids as a new landmark in atherosclerosis

Cited by 93 publications

References 168 publications

Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

Oxidized Low-Density Lipoprotein-Binding Specificity of the Asp-Hemolysin-Related Synthetic Peptides from Aspergillus fumigatus

A Synthetic Peptide (P-21) Derived from Asp-Hemolysin Inhibits the Induction of Macrophage Proliferation by Oxidized Low-Density Lipoprotein

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