Altered distribution of plasma PAF-AH between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus

Kujiraoka, Takeshi; Iwasaki, Takashi; Ishihara, Misa; Ito, Mayumi; Nagano, Makoto; Kawaguchi, Akito; Takahashi, Sadao; Ishi, Jun; Tsuji, Masahiro; Egashira, Tohru; Stepanova, I. P.; Miller, N. E.; Hashimoto, Hiroaki

doi:10.1194/jlr.d300021-jlr200

Cited by 46 publications

(35 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Genomic DNA was extracted as previously described (Yoshida et al 2002). Of the 120 subjects exhibiting Lp-PLA2 deficiency, 119 were found to carry a mutant allele of Lp-PLA2 that is common in Japan-V279F (Kujiraoka et al 2003).…”

Section: Patients and Clinical Profilesmentioning

confidence: 99%

“…LDL cholesterol was calculated according to the Friedewald formula (Friedewald et al 1972). Plasma Lp-PLA2 (PAF-AH) activity was determined using [ 3 H] PAF, and Lp-PLA2 mass concentration was determined by sandwich enzyme-linked immunosorbent assay (ELISA) as described by Kujiraoka et al (2003). Genomic DNA was extracted as previously described (Yoshida et al 2002).…”

Section: Patients and Clinical Profilesmentioning

confidence: 99%

“…Site-directed mutagenesis and transfection of COS-7 cells for V279F, Q281R, and I317N mutant alleles A cDNA fragment encoding amino acids 42-441 of Lp-PLA2 was obtained by RT-PCR from mRNA expressed by peripheral monocyte-derived macrophages and subcloned into the mammalian expression vector pcDNA3.1(+) (Invitrogen, CA, USA) in the manner described by Kujiraoka et al (2003). Mutant cDNAs (V279F, Q281R, and I317N) were generated from the pcDNA3.1(+)/Lp-PLA2 vector using QuickChange XL Site-Directed Mutagenesis Kits (Stratagene) according to the manufacturer's instructions.…”

Section: Patients and Clinical Profilesmentioning

confidence: 99%

“…After incubation, the beads were precipitated by centrifugation and washed three times with 0.1% Tween20 (Nakalai Tesque) containing PBS, resuspended in SDS-PAGE sample buffer, heated to 95°C for 5 min, and then subjected to SDS-PAGE. After electrophoresis, the proteins were transferred to PVDF membranes (Millipore), and Western blotting was performed using a polyclonal antibody that had been raised in rabbits against recombinant human Lp-PLA2 expressed by E. coli (Kujiraoka et al 2003), and goat HRP antirabbit IgG (Zymed). Detection was achieved by means of Western Lightning Chemiluminescence Reagent (PerkinElmer) according to manufacturer recommendations.…”

Section: Western-blot Analysismentioning

confidence: 99%

“…About 80% of the Lp-PLA2 in plasma is bound to LDL via specific interaction between the C-terminus of apoB-100, the major constitutive protein of the LDL particle, and two domains of Lp-PLA2, one around tyrosine 205 and the other around tryptophan 115-leucine 116. The rest of the plasma Lp-PLA2 is bound to HDL and VLDL (Stafforini et al 1999;Kujiraoka et al 2003). The Lp-PLA2 enzyme is also known as platelet-activating factor (PAF) acetylhydrolase (PAF-AH), since one of its known functions is to deactivate PAF (Stafforini et al 1987a,b).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

Ishihara¹,

Iwasaki²,

Nagano³

et al. 2004

J Hum Genet

Self Cite

View full text Add to dashboard Cite

Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor (PAF) acetylhydrolase (PAF-AH), is a member of the serine-dependent class of A2 phospholipases that hydrolyze sn2-ester bonds of fragmented or oxidized phospholipids at sites where atherosclerotic plaques are forming. Most circulating Lp-PLA2 is bound to lowdensity lipoprotein (LDL) particles in plasma and the rest to high-density lipoprotein (HDL). Deficiency of Lp-PLA2 is a predisposing factor for cardiovascular diseases in the Japanese population. We describe here two novel mutations of the gene encoding Lp-PLA2, InsA191 and I317N in Japanese subjects. The first patient, with partial Lp-PLA2 deficiency, was heterozygous for the InsA191 mutation; macrophages from this patient secreted only half the normal amount of Lp-PLA2 in vitro. The other patient, who showed complete Lp-PLA2 deficiency, was a compound heterozygote for the novel I317N mutation and a common V279F mutation; macrophages from that patient failed to secrete any Lp-PLA2. Measurement of Lp-PLA2 mass, activity and Western blotting verified impaired production and secretion of the enzyme after transfection of mutant construct into COS-7 cells. These results indicated that both novel mutants, InsA191 and I317N, impair function of the Lp-PLA2 gene.

show abstract

Section: Patients and Clinical Profilesmentioning

confidence: 99%

Section: Patients and Clinical Profilesmentioning

confidence: 99%

Section: Patients and Clinical Profilesmentioning

confidence: 99%

Section: Western-blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

Ishihara¹,

Iwasaki²,

Nagano³

et al. 2004

J Hum Genet

Self Cite

View full text Add to dashboard Cite

show abstract

Effect of fortified milk on lyso‐platelet‐activating factor acetyltranferase and lipoprotein‐associated phospholipase A₂ in hypercholesterolemic adults

Ntzouvani

Nomikos

Petrogianni

et al. 2013

Euro J Lipid Sci & Tech

View full text Add to dashboard Cite

Hypercholesterolemia is associated with subclinical inflammation, characterised by elevated proinflammatory mediators. Lyso-platelet-activating factor acetyltransferase (lyso-PAF AT) and lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) are two key metabolic enzymes of platelet-activating factor (PAF), a potent inflammatory lipid mediator. Little information is available concerning the efficacy of a dietary intervention on the metabolism of PAF. The objective of the study was to evaluate the effect of fortified milk on the activity of these enzymes. Forty-three adults (mean age 49.8 AE 8.1 years) with body mass index < 35 kg/m 2 , and total cholesterol >200 but < 310 mg/dL were randomised to two groups; (i) intervention group received 500 mL/day (two glasses) of a low-fat milk fortified with phytosterols, linoleic and alpha linolenic acids, vitamin C, vitamin E, vitamin A, vitamin B6, vitamin B12, folic acid, magnesium and selenium (n ¼ 22), and (ii) placebo group received 500 mL/day of a conventional low-fat milk (n ¼ 21) for 3 months. Outcome measures were the activities of lyso-PAF AT from leukocytes and serum Lp-PLA 2 determined with established methods. None of the activities changed significantly during the study in the intervention group, lyso-PAF AT (95% confidence interval: À1.7, 2.3 nmol/min/mg; p ¼ 0.246), and Lp-PLA 2 (À7.8, 5.8 nmol/min/mL, p ¼ 0.591). No difference was observed between the two groups. In conclusion, daily intake of two glasses of phytosterols, antioxidants, linoleic and linolenic acids via fortified milk for three months had no effect on the activity of either lyso-PAF AT or Lp-PLA 2 .Practical applications: Platelet-activating factor (PAF) was the first intact phospholipid known to have messenger functions in which the signaling results from the molecule binding to specific receptors on the plasma membrane or other membranes of the cell. It has a number of pro-inflammatory properties, and affects several critical points of atherogenesis including thrombosis, inflammation, and oxidation. Fortification of milk with nutrients that possess anti-inflammatory properties and administration to adults with elevated blood cholesterol could provide a means to controlling inflammatory process through the synthesis and degradation of PAF in a population group at risk for cardiovascular morbidity and mortality.

show abstract

The inverse relation of HDL anti‐oxidative functionality with serum amyloid a is lost in metabolic syndrome subjects

Dullaart

Boer

Annema

et al. 2013

Obesity

View full text Add to dashboard Cite

Objective: Anti-oxidative properties of high density lipoproteins (HDL) are relevant for atheroprotection. HDL carry serum amyloid A (SAA), which may impair HDL functionality. We questioned whether HDL antioxidative capacity is determined by SAA. Design and Methods: Relationships of HDL anti-oxidative capacity (% inhibition of low density lipoprotein oxidation in vitro) with SAA were determined in 54 non-diabetic subjects without metabolic syndrome (MetS) and 68 subjects with MetS (including 51 subjects with Type 2 diabetes mellitus). Results: SAA levels were higher in MetS subjects, coinciding higher high sensitive C-reactive protein (hs-CRP) and lower HDL cholesterol and apolipoprotein (apo) A-I levels (P<0.001 for all). HDL anti-oxidative capacity was not different between subjects with and without MetS (P¼0.76), but the HDL anti-oxidation index (HDL anti-oxidative capacity multiplied by individual HDL cholesterol concentrations), as a measure of global anti-oxidative functionality of HDL, was lower in Mets subjects (P<0.001). HDL anti-oxidative capacity was correlated inversely with SAA levels in subjects without MetS (r¼-0.286, P¼0.036). Notably, this relationship was independent of HDL cholesterol or apoA-I (P<0.05 for both). In contrast, no relation of HDL anti-oxidative capacity with SAA was observed in MetS subjects (r¼0.032, P¼0.80). The relationship of SAA with HDL anti-oxidative capacity was different in subjects with MetS compared to subjects without MetS (P¼0.039 for the interaction between the presence of MetS and SAA on HDL antioxidative capacity) taking age and diabetes status into account. Conclusion: Higher SAA levels may impair HDL anti-oxidative functionality. The relationship of this physiologically relevant HDL functionality measure with circulating SAA levels is apparently disturbed in metabolic syndrome.

show abstract

Altered distribution of plasma PAF-AH between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus

Cited by 46 publications

References 38 publications

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

Effect of fortified milk on lyso‐platelet‐activating factor acetyltranferase and lipoprotein‐associated phospholipase A₂ in hypercholesterolemic adults

The inverse relation of HDL anti‐oxidative functionality with serum amyloid a is lost in metabolic syndrome subjects

Contact Info

Product

Resources

About

Altered distribution of plasma PAF-AH between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus

Cited by 46 publications

References 38 publications

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

Effect of fortified milk on lyso‐platelet‐activating factor acetyltranferase and lipoprotein‐associated phospholipase A2 in hypercholesterolemic adults

The inverse relation of HDL anti‐oxidative functionality with serum amyloid a is lost in metabolic syndrome subjects

Contact Info

Product

Resources

About

Effect of fortified milk on lyso‐platelet‐activating factor acetyltranferase and lipoprotein‐associated phospholipase A₂ in hypercholesterolemic adults