High-density lipoprotein profile in newly-diagnosed lower extremity artery disease in Slovak population without diabetes mellitus.

OBJECTIVE: To assess the relationship of high density lipoprotein subfractions to newly-diagnosed lower extremity artery disease (LEAD) in individuals without diabetes mellitus and without hypolipidemic therapy. METHODS: This cross-sectional study involves 106 subjects: 51 had newly diagnosed LEAD and no diabetes anamnesis and were not on hypolipidemic therapy; and 55 controls were without clinical presentation of LEAD and were normolipidemic. Analysis of HDL subclasses was performed by an innovative electrophoresis method on polyacrylamide gel (PAG), the Lipoprint HDL System. RESULTS: In LEAD subjects, total HDL-C levels as well as HDL2 (intermediate-to-large particles) subfraction levels were decreased (p<0.0001 and p<0.019 respectively). Interestingly the HDL3 (small particles) subfraction was significantly higher and lost its proportional relationship within the HDL cholesterol fraction (p<0.025, p<0.01 respectively). CONCLUSION: These findings pointed out that: (i) the reduction of HDL-C and especially HDL2 subpopulation opposite to the increase of small HDL3 subclass may be considered as important predictors of cardiovascular diseases. (ii) there are undisputable advantages of using Lipoprint HDL to identify HDL subfractions; the presence of high concentration of small HDL in patients with PAD/LEAD emphasizes that the potentially proatherogenic subclass of HDL family is linked to small HDL.

Glycemic control and high-density lipoprotein characteristics in adolescents with type 1 diabetes.

BACKGROUND: Recent evidence suggests that high-density lipoprotein (HDL) physicochemical characteristics and functional capacity may be more important that HDL-C levels in predicting coronary heart disease. There is little data regarding HDL subclasses distribution in youth with type 1 diabetes. OBJECTIVE: To assess the relationships between glycemic control and HDL subclasses distribution, composition, and function in adolescents with type 1 diabetes. METHODS: This cross-sectional study included 52 adolescents with type 1 diabetes aged 12-16 years and 43 age-matched non-diabetic controls. Patients were divided into two groups: one in fair control [hemoglobin A1c (HbA1c) < 9.6%] and the second group with poor glycemic control (HbA1c ≥ 9.6%). In all participants, we determined HDL subclasses distribution, composition, and the ability of plasma and of isolated HDL to promote cellular cholesterol efflux. Levels of soluble adhesion molecules were also measured. RESULTS: Although both groups of patients and the control group had similar HDL-C levels, linear regression analyses showed that compared with non-diabetic subjects, the poor control group had a lower proportion of HDL2b subclass (p = 0.029), triglyceride enriched (p = 0.045), and cholesteryl ester depleted (p = 0.028) HDL particles. Despite these HDL changes, cholesterol efflux was comparable among the three groups. The poor control group also had significantly higher intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 plasma concentrations. CONCLUSIONS: In adolescents with type 1 diabetes, poor glycemic control is associated with abnormalities in HDL subclasses distribution and HDL lipid composition, however, in spite of these HDL changes, the ability of HDL to promote cholesterol efflux remains comparable to that of healthy subjects.

Activation of lipoprotein lipase increases serum high density lipoprotein 2 cholesterol and enlarges high density lipoprotein 2 particles in rats.

It is known that postheparin plasma lipoprotein lipase (LPL) activity correlates with serum high density lipoprotein cholesterol (HDL-C) levels in humans and animals. Furthermore, LPL has been reported to cause enlargement of HDL particle size in vitro. However, these effects have not yet been experimentally proven. The aim of this study was to determine whether LPL has a role in increase in HDL-C and enlargement of HDL particle by activating the LPL function with NO-1886, the LPL promoting agent. NO-1886 administration increased postheparin plasma LPL activity without influencing hepatic triglyceride lipase activity. NO-1886 increased serum HDL(2)-cholesterol (HDL(2)-C) concentration and enlarged HDL(2) particle size, but did not increase serum HDL(3)-cholesterol concentration or enlarge HDL(3) particle size. Also, serum HDL(2)-C concentrations were positively correlated with HDL(2) particle size (r=0.910). Our study demonstrates that the LPL activation induced with NO-1886 may cause production of HDL(2)-C by catabolism of triglyceride-rich lipoproteins and enlarges HDL(2) particle size in rats.

The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution.

OBJECTIVE: To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. METHODS: Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. RESULTS: Contents of preß1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preß1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of preß1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. CONCLUSIONS: The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preß1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.

Effect of HDL composition and particle size on the resistance of HDL to the oxidation.

OBJECTIVES: To study the resistance of HDL particles to direct oxidation in respect to the distribution of HDL particles. DESIGN AND METHODS: We studied HDL composition, subclass distribution, and the kinetics of CuSO4-induced oxidation of total HDL and HDL3 in vitro in 36 low-HDL-C subjects and in 41 control subjects with normal HDL-C. RESULTS: The resistance of HDL3 to oxidation, as assessed from the propagation rate was significantly higher than that of total HDL. The propagation rate and diene formation during HDL oxidation in vitro was attenuated in HDL derived from low-HDL-C subjects. Propagation rate and maximal diene formation during total HDL oxidation correlated significantly with HDL mean particle size. The propagation rate of total HDL oxidation in vitro displayed a significant positive association with HDL2 particle mass and HDL mean particle size by multiple regression analyses. CONCLUSIONS: These observations highlight that the distribution of HDL subpopulations has important implications for the potential of HDL as an anti-oxidant source.

Severely modified lipoprotein properties without a change in cholesteryl ester transfer protein activity in patients with acute renal failure secondary to Hantaan virus infection.

Patients with hemorrhagic fever with renal syndrome (HFRS) often exhibit altered serum lipid and lipoprotein profile during the oliguric phase of the disease. Serum lipid and lipoprotein profiles were assessed during the oliguric and recovery phases in six male patients with HFRS. In the oliguric phase of HFRS, the apolipoprotein (apo) C-III content in high-density lipoproteins (HDL) was elevated, whereas the apoA-I content was lowered. The level of expression and activity of antioxidant enzymes were severely reduced during the oliguric phase, while the cholesteryl ester transfer protein activity and protein level were unchanged between the phases. In the oliguric phase, electromobility of HDL2 and HDL3 was faster than in the recovery phase. Low-density lipoprotein (LDL) particle size was smaller and the distribution was less homogeneous. Patients with HFRS in the oliguric phase had severely modified lipoproteins in composition and metabolism.

Postprandial lipemia enhances the capacity of large HDL2 particles to mediate free cholesterol efflux via SR-BI and ABCG1 pathways in type IIB hyperlipidemia.

Lipid and cholesterol metabolism in the postprandial phase is associated with both quantitative and qualitative remodeling of HDL particle subspecies that may influence their anti-atherogenic functions in the reverse cholesterol transport pathway. We evaluated the capacity of whole plasma or isolated HDL particles to mediate cellular free cholesterol (FC) efflux, cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer, and selective hepatic CE uptake during the postprandial phase in subjects displaying type IIB hyperlipidemia (n = 16). Postprandial, large HDL2 displayed an enhanced capacity to mediate FC efflux via both scavenger receptor class B type I (SR-BI)-dependent (+12%; P < 0.02) and ATP binding cassette transporter G1 (ABCG1)-dependent (+31%; P < 0.008) pathways in in vitro cell systems. In addition, the capacity of whole postprandial plasma (4 h and 8 h postprandially) to mediate cellular FC efflux via the ABCA1-dependent pathway was significantly increased (+19%; P < 0.0003). Concomitantly, postprandial lipemia was associated with elevated endogenous CE transfer rates from HDL2 to apoB lipoproteins and with attenuated capacity (-17%; P < 0.02) of total HDL to deliver CE to hepatic cells. Postprandial lipemia enhanced SR-BI and ABCG1-dependent efflux to large HDL2 particles. However, postprandial lipemia is equally associated with deleterious features by enhancing formation of CE-enriched, triglyceride-rich lipoprotein particles through the action of CETP and by reducing the direct return of HDL-CE to the liver.

FT-IR spectroscopy of lipoproteins--a comparative study.

FT-IR spectra, in the frequency region 4000-600 cm(-1), of four major lipoprotein classes: very low density lipoprotein (VLDL), low density lipoprotein (LDL) and two subclasses of high density lipoproteins (HDL(2) and HDL(3)) were analyzed to obtain their detailed spectral characterization. Information about the protein domain of particle was obtained from the analysis of amide I band. The procedure of decomposition and curve fitting of this band confirms the data already known about the secondary structure of two different apolipoproteins: apo A-I in HDL(2) and HDL(3) and apo B-100 in LDL and VLDL. For information about the lipid composition and packing of the particular lipoprotein the well expressed lipid bands in the spectra were analyzed. Characterization of spectral details in the FT-IR spectrum of natural lipoprotein is necessary to study the influence of external compounds on its structure.

Distinct HDL subclasses present similar intrinsic susceptibility to oxidation by HOCl.

The heme protein myeloperoxidase (MPO) functions as a catalyst for lipoprotein oxidation. Hypochlorous acid (HOCl), a potent two-electron oxidant formed by the MPO-H(2)O(2)-chloride system of activated phagocytes, modifies antiatherogenic high-density lipoprotein (HDL). The structural heterogeneity and oxidative susceptibility of HDL particle subfractions were probed with HOCl. All distinct five HDL subfraction were modified by HOCl as demonstrated by the consumption of tryptophan residues and free amino groups, cross-linking of apolipoprotein AI, formation of HOCl-modified epitopes, increased electrophoretic mobility and altered content of unsaturated fatty acids in HDL subclasses. Small, dense HDL3 were less susceptible to oxidative modification than large, light HDL2 on a total mass basis at a fixed HOCl:HDL mass ratio of 1:32, but in contrast not on a particle number basis at a fixed HOCl:HDL molar ratio of 97:1. We conclude that structural and physicochemical differences between HDL subclasses do not influence their intrinsic susceptibility to oxidative attack by HOCl.

The specific amino acid sequence between helices 7 and 8 influences the binding specificity of human apolipoprotein A-I for high density lipoprotein (HDL) subclasses: a potential for HDL preferential generation.

Humans have two major high density lipoprotein (HDL) sub-fractions, HDL(2) and HDL(3), whereas mice have a monodisperse HDL profile. Epidemiological evidence has suggested that HDL(2) is more atheroprotective; however, currently there is no direct experimental evidence to support this postulate. The amino acid sequence of apoA-I is a primary determinant of HDL subclass formation. The majority of the alpha-helical repeats in human apoA-I are proline-punctuated. A notable exception is the boundary between helices 7 and 8, which is located in the transitional segment between the stable N-terminal domain and the C-terminal hydrophobic domain. In this study we ask whether the substitution of a proline-containing sequence (PCS) separating other helices in human apoA-I for the non-proline-containing sequence (NPCS) between helices 7 and 8 (residues 184-190) influences HDL subclass association. The human apoA-I mutant with PCS2 replacing NPCS preferentially bound to HDL(2). In contrast, the mutant where PCS3 replaced NPCS preferentially associated with HDL(3). Thus, the specific amino acid sequence between helices 7 and 8 influences HDL subclass association. The wild-type and mutant proteins exhibited similar physicochemical properties except that the two mutants displayed greater lipid-associated stability versus wild-type human apoA-I. These results focus new attention on the influence of the boundary between helices 7 and 8 on the properties of apoA-I. The expression of these mutants in mice may result in the preferential generation of HDL(2) or HDL(3) and allow us to examine experimentally the anti-atherogenicity of the HDL subclasses.