BACKGROUND/OBJECTIVES: OxLDL-β2GPI complex has been suggested to have a role in the development of atherosclerosis and other inflammatory diseases. The aim of this study was to investigate the possible association of circulating oxLDL-β2GPI with obesity-induced inflammatory state of adipose tissue and related comorbidities as metabolic syndrome development. SUBJECTS/METHODS: Two cohorts of subjects were examined in the study. Cohort I: 36 women with wide range of body mass index (17-48 kg m-2) and metabolic status (with or without metabolic syndrome (MS); cohort II: 20 obese women undergoing a dietary intervention (DI) consisting of 1-month very-low-calorie diet, and 5 months of weight-stabilization period. Serum levels of oxLDL-β2GPI were measured by enzyme-linked immunosorbent assay. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp and homeostasis model assessment of insulin resistance. mRNA expression of macrophage markers was determined in both subcutaneous (SAT) and visceral (VAT) adipose tissue in cohort I and in SAT in cohort II. RESULTS: Serum oxLDL-β2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17±1.97, P<0.001; vs obese without MS: 16.36±2.89, P<0.05). Serum oxLDL-β2GPI correlated with MS indices (glucose, high-density lipoprotein, triglyceride and ureic acid) and with mRNA expression of macrophage markers in VAT. Weight-reducing DI decreased serum oxLDL-β2GPI levels together with lipid parameters and the mRNA expression of inflammatory markers in SAT. CONCLUSIONS: OxLDL-β2GPI seems to be an important marker of visceral adipose tissue inflammation and possibly a factor contributing to insulin resistance and metabolic syndrome development in obese patients.
- MeSH
- beta-2-glykoprotein I krev chemie metabolismus MeSH
- biologické markery krev MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny LDL krev chemie metabolismus MeSH
- metabolický syndrom krev patofyziologie MeSH
- multiproteinové komplexy MeSH
- obezita * krev metabolismus patofyziologie MeSH
- tuková tkáň metabolismus patofyziologie MeSH
- zánět krev patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
By means of fluorescence spectroscopy we have studied the kinetics of interaction of a photosensitizer hypericin (Hyp) with high-density lipoproteins (HDL). Hyp is incorporated into HDL molecules as monomer till ratio Hyp/HDL ∼8:1 and above this ratio forms non-fluorescent aggregates. This number is different from that found in the case of Hyp incorporation into low-density lipoprotein (LDL) molecules (8:1 vs 30:1). The difference is mainly attributed to the smaller size of HDL in comparison with LDL molecule. Biphasic kinetics of Hyp association with HDL was observed. The rapid phase of incorporation is completed within seconds, while the slow one lasts several minutes. The kinetics of the association of Hyp molecules with free HDL, Hyp/HDL=10:1 complex and the redistribution of Hyp from Hyp/HDL=70:1 complex to free HDL molecules reveal a qualitative similar characteristics of these processes with those observed for the interaction of Hyp with LDL. However, the incorporation of Hyp into HDL in the "slow" phase is more rapid than to LDL and extend of Hyp penetration into lipoproteins in the fast phase is also much higher in the case of HDL. The lower concentration of cholesterol molecules in outer shell of HDL particles is probably the determining factor for the more rapid kinetics of Hyp incorporation to and redistribution from these molecules when comparing with LDL particles.
- MeSH
- buněčné linie MeSH
- chemie farmaceutická MeSH
- fluorescenční spektrometrie MeSH
- fotosenzibilizující látky chemie MeSH
- lipoproteiny HDL chemie MeSH
- lipoproteiny LDL chemie MeSH
- perylen analogy a deriváty chemie MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE OF REVIEW: Subfractions of LDL and HDL defined by differences in particle size and density have been associated to varying degrees with risk of cardiovascular disease (CVD). Assessment of these relationships has been clouded by lack of standardization among the various analytic methodologies as well as the strong correlations of the subfractions with each other and with standard lipid and lipoprotein risk markers. This review summarizes the properties of the major LDL and HDL particle subclasses, and recent evidence linking their measurement with risk of atherosclerosis and CVD. RECENT FINDINGS: Several recent studies have shown independent relationships of levels of LDL and HDL-size subclasses to risk of both coronary artery and cerebrovascular disease. However, the two largest studies, employing nuclear magnetic resonance and ion mobility, respectively, did not find evidence that these measurements improved risk assessment compared with standard lipoprotein assays. In the latter study, principal component analysis was used to group multiple subfraction measurements into three distinct and statistically independent clusters that were related both to cardiovascular outcomes and to genotypes that may reflect underlying metabolic determinants. SUMMARY: Although there is as yet inconclusive evidence as to the extent to which LDL and HDL subfraction measurements improve clinical assessment of CVD risk beyond standard lipid risk markers, recent studies suggest that more refined analyses of lipoprotein subspecies may lead to further improvements in CVD risk evaluation and particularly in identification of appropriate targets for therapeutic intervention in individual patients.
- MeSH
- kardiovaskulární nemoci metabolismus MeSH
- lidé MeSH
- lipoproteiny HDL chemie klasifikace metabolismus MeSH
- lipoproteiny LDL chemie klasifikace metabolismus MeSH
- lipoproteiny chemie klasifikace metabolismus MeSH
- náchylnost k nemoci MeSH
- riziko MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Platelets play a key role in thrombotic vascular occlusion at the side of an atherosclerotic plaque. Malondialdehyde (MDA) derivatives are components of oxidized LDL. Recent studies suggest enhanced adhesion of platelets on oxidized LDL, but evidence of MDA-modified LDL contribution to enhanced platelet adhesion is missing. The aim of this study was to investigate platelet adhesion on LDLs with various content of MDA and to analyze its physiological relevance. LDLs were isolated by hydroxyapatite chromatography then analyzed. MDA, vitamin E and vitamin A content was estimated by HPLC methods and adhesion of platelets on modified LDLs was assessed. Both MDA and hypochlorite reactions induced an increase of both malondialdehyde content and negative charge in LDLs preparations. In LDLs of iron-overloaded patients both MDA content and negative charge was also significantly increased. The analysis of data showed that enhanced negative charge of LDLs had only negligible influence on platelet adhesion. The binding of platelets on LDL particles modified by MDA resulted in an S-shape curve and was substantially enhanced by high levels of MDA in LDL preparations. Malondialdehyde content both in hypochlorite modified LDLs and in LDLs of iron-overloaded patient matched the lower part of the binding curve. The platelet adhesion on circulating LDLs modified in in vivo conditions of oxidation stress in blood of iron-overloaded patients depends with considerable certainty preferably on non-MDA derived changes in derivatized LDLs. On the other hand, oxidized LDLs in atherosclerotic lesions can be much more extensively modified by MDA resulting in surfaces with enhanced affinity to adhering platelets. Such LDLs may be accessible to platelets, due to endothelial denudation or plaque rupture.
- MeSH
- adhezivita trombocytů fyziologie účinky léků MeSH
- časové faktory MeSH
- chromatografie MeSH
- financování organizované MeSH
- kyselina chlorná farmakologie MeSH
- lidé MeSH
- lipoproteiny LDL fyziologie chemie izolace a purifikace MeSH
- malondialdehyd farmakologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny LDL fyziologie chemie krev MeSH
- lipoproteiny VLDL fyziologie chemie krev MeSH
- menopauza MeSH
- peroxidace lipidů MeSH
- protilátky krev MeSH
- tuková tkáň MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- cévní endotel fyziologie účinky léků MeSH
- chemotaxe leukocytů genetika účinky léků MeSH
- exprese genu účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- lipoproteiny LDL chemie metabolismus škodlivé účinky MeSH
- messenger RNA fyziologie MeSH
- oxidace-redukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- ateroskleróza diagnóza etiologie MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidové peroxidy MeSH
- lipoproteiny LDL chemie imunologie metabolismus MeSH
- metabolické nemoci imunologie komplikace krev MeSH
- oxidace-redukce MeSH
- protilátky krev MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- MeSH
- ateroskleróza metabolismus prevence a kontrola MeSH
- koronární nemoc metabolismus prevence a kontrola MeSH
- lipoproteiny HDL fyziologie chemie krev MeSH
- lipoproteiny LDL fyziologie chemie krev MeSH
- lipoproteiny VLDL fyziologie chemie krev MeSH
- lipoproteiny fyziologie chemie krev MeSH
- rizikové faktory MeSH
- Publikační typ
- přehledy MeSH
