Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents.

BACKGROUND: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children. METHODS: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters. RESULTS: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (ρ = -0.423; p = 0.025) in the group with hypertension. CONCLUSIONS: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.

Comparative Studies of the Structural and Physicochemical Properties of the First Fullerene Derivative FD-C60 (Fullerenol) and Second Fullerene Derivate SD-C60 (3HFWC).

In order to maximally reduce the toxicity of fullerenol (the first derivative of C60, FD-C60), and increase its biomedical efficiency, the second derivative SD-C60 (3HFWC, Hyper-Harmonized Hydroxylated Fullerene Water Complex) was created. Several different methods were applied in the comparative characterization of FD-C60 and SD-C60 with the same OH groups in their core. FD-C60 as an individual structure was about 1.3 nm in size, while SD-C60 as an individual structure was 10-30 nm in size. Based on ten physicochemical methods and techniques, FD-C60 and SD-C60 were found to be two different substances in terms of size, structure, and physicochemical properties; FD-C60, at 100 °C, had endothermic characteristics, while SD-C60, at 133 °C, had exothermic characteristics; FD-C60 did not have water layers, while SD-C60 had water layers; the zeta potential of FD-C60 was -25.85 mV, while it was -43.29 mV for SD-C60. SD-C60 is a promising substance for use in cosmetics and pharmaceuticals.

Antioxidant status in hypertensive disorders of pregnancy.

OBJECTIVE: Pregnancy can be associated with maternal hypertension leading to possible complications in pregnancy outcome. Antioxidant status may be proned to changes during pregnancy with hypertension. The aim of our study was to estimate antioxidant status through high-risk pregnancies. METHODS: Seventy-nine pregnant women with high-risk for preeclampsia development were included and 46 of them developed some hypertensive disorder in pregnancy. Superoxide-dismutase (SOD) and paraoxonase 1 (PON1) activities and relative proportion of PON1 activiity on different HDL subclasses were determined in 1st, 2nd, and 3rd trimester and prior to delivery. RESULTS: SOD activity was significantly lower in 2nd and 3rd trimesters when compared to 1st trimester (P˂0.001) whereas PON1 activity was significantly higher in 3rd than in 1st trimester (P˂0.05) in group of hypertensive women. This group had significantly higher SOD and PON1 activities and relative proportion of PON1 on HDL3c subclasses in the 1st trimester, significantly increased PON1 in the 3rd trimester and prior to delivery and significantly higher PON1 activity on HDL3c subclasses (P˂0.05) than nonhypertensive group. In 1st trimester and prior to delivery, total PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant ability to mark out hypertension in pregnancy (P˂0.05). CONCLUSIONS: SOD activity decreased whereas total PON1 activity increased during pregnancy with hypertension. Pregnant women with hypertension had higher activities of PON1 and SOD and relative proportion of PON1 on HDL3c subclasses than nonhypertensive ones. PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant association with hypertension in pregnancy.

Unraveling the role of oxidative stress and lipid status parameters in the onset of preeclampsia.

OBJECTIVE: The aim of the study was to assess the potential role of oxidative stress and lipid status in the onset of preeclampsia.METHODS: 138 high-risk pregnant women were prospectively followed. Assessment of oxidative stress (TAS, TOS, AOPP and SH groups) and lipid status (t-C, LDL-C, HDL-C, TGC, APO-A1, APO-B) was carried out during the pregnancy.RESULTS: 30 women developed preeclampsia. TGC, atherogenic index of plasma, TAS and SH levels were higher in women who subsequently developed preeclampsia (p<0.05).CONCLUSION: Oxidative stress and lipid status disturbance have a potential role in the onset of preeclampsia in high risk pregnancies.

Effect of propolis and N-acetylcysteine supplementation on lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection.

BACKGROUND: Propolis and N-acetylcysteine have positive impact on respiratory tract health. Also, it has been suggested that they have beneficial effects on serum lipid and oxidative stress status, but the available data are limited and mostly gained from animal models. In this study we evaluated the effects of propolis and N-acetylcysteine supplementation (PropoMucil®) on lipid status, lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection. METHODS: Twenty subjects with acute respiratory infection were included. PropoMucil® granules for oral solution (80 mg of dry propolis extract and 200 mg of N-acetylcysteine) were administered tree times per day for ten days. Serum lipid profile, paraoxonase 1 activity and low-density and high-density lipoprotein size and subclasses distribution were assessed at baseline and after supplementation. RESULTS: Following ten days of supplementation lipid status remained unchanged, but a significant increase of low-density lipoprotein particle size and proportion of high-density lipoprotein 3a particles were found (P<0.05). Moreover, supplementation with PropoMucil® significantly improved high-density lipoprotein particles distribution, particularly in those who smoke. There was a moderate increase of paraoxonase 1 activity, but without statistical significance. CONCLUSIONS: The presented study demonstrated that short-term supplementation with PropoMucil® has beneficial effects on low-density and high-density lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection particularly in those who smoke.

Increased Oxidized High-Density Lipoprotein/High-Density Lipoprotein-Cholesterol Ratio as a Potential Indicator of Disturbed Metabolic Health in Overweight and Obese Individuals.

BACKGROUND: We evaluated the qualitative characteristics of high-density lipoprotein (HDL) particles in metabolically healthy and unhealthy overweight and obese subjects. METHODS: The study involved 115 subject individuals classified as metabolically healthy and unhealthy, as in overweight and obese groups. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure oxidized HDL (OxHDL) and serum amyloid A (SAA) concentrations. Lipoprotein subfractions were separated using nondenaturing gradient gel electrophoresis. RESULTS: An independent association was shown between increased OxHDL/HDL-cholesterol ratio and the occurrence of metabolically unhealthy phenotype in the overweight and obese groups. The OxHDL/HDL-cholesterol ratio showed excellent and acceptable diagnostic accuracy in determination of metabolic health phenotypes (overweight group, AUC = 0.881; obese group, AUC = 0.765). Accumulation of smaller HDL particles in metabolically unhealthy subjects was verified by lipoprotein subfraction analysis. SAA concentrations did not differ significantly between phenotypes. CONCLUSIONS: Increased OxHDL/HDL-cholesterol ratio may be a potential indicator of disturbed metabolic health in overweight and obese individuals.

Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control.

BACKGROUND AND AIMS: Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control. METHODS: Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 ±â€¯3.0 years and treated by intensive insulin therapy. RESULTS: Plasma PCSK9 levels significantly increased with worsening of glycemic control (p < 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p < 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p < 0.001), but negatively with HDL size (p < 0.05). CONCLUSIONS: The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.

Association of acute Babesia canis infection and serum lipid, lipoprotein, and apoprotein concentrations in dogs.

BACKGROUND: Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. HYPOTHESIS: Dogs with B. canis-induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. ANIMALS: Twenty-nine client-owned dogs with acute B. canis infection and 10 clinically healthy control dogs. METHODS: Observational cross-sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA-1 (radioimmunoassay) and SAA was determined. RESULTS: Dogs with B. canis infection had a marked APR (median SAA, 168.3 µg/mL; range, 98.1-716.2 µg/mL) compared with controls (3.2 µg/mL, 2.0-4.2 µg/mL) (P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89-7.64 mmol/L versus 6.15 mmol/L, 4.2-7.4 mmol/L) (P = .02), phospholipid (4.64 mmol/L, 2.6-6.6 mmol/L versus 5.72 mmol/L, 4.68-7.0 mmol/L) (P = .02), and α-lipoproteins (77.5%, 27.7%-93.5% versus 89.2%, 75.1%-93.5%) (P = .04), and higher ApoA-1 (1.36 U, 0.8-2.56 U versus 0.95 U, 0.73-1.54 U) concentrations (P = .02). Serum amyloid A correlated with high-density lipoproteins (HDLs) diameter (rho = .43; P = .03) and ApoA-1 (rho = .63, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Major changes associated with B. canis-induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA-1 and SAA concentration increase is a unique still unexplained pathophysiological finding.

Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development.

INTRODUCTION: Dyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy. MATERIALS AND METHODS: This case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods. RESULTS: Total cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P < 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P < 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P < 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%). CONCLUSIONS: Patients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development.

Effects of co-existing autoimmune diseases on serum lipids and lipoprotein subclasses profile in paediatric patients with type 1 diabetes mellitus.

OBJECTIVE: Paediatric patients with type 1 diabetes mellitus (T1DM) frequently develop other autoimmune disorders; most commonly autoimmune thyroiditis (ATD) and celiac disease (CD). In this study we evaluated whether co-existing autoimmune diseases had significant impact on lipid and lipoprotein subclasses, as known cardiovascular risk factors in T1DM. DESIGN AND METHODS: Study included 201 subjects with T1DM (14.1 ±â€¯2.9 years) and 141 age- and gender-matched controls. ATD was presented in 30 and CD in 15 T1DM patients. Serum lipid parameters were determined by routine laboratory methods and plasma low-density (LDL) and high-density lipoprotein (HDL) subclasses by gradient-gel electrophoresis method. RESULTS: Both groups of T1DM patients with concomitant autoimmune disease had significantly lower HDL-C levels (P < 0.05) than the patients with T1DM only, but comparable to control group (P = 0.436). T1DM patients had significantly higher (P < 0.001) proportion of small HDL subclasses than controls. Mean value of atherosclerosis index in patients with T1DM + CD was the highest (1.75 ±â€¯0.86) and it was significantly higher than the index in patients with T1DM only (1.33 ±â€¯0.51; P < 0.05). LDL size did not differ between the groups of T1DM patients and control group (P = 0.619). The size of HDL particles was significantly reduced (P < 0.05) in the groups with associated autoimmune diseases. The patients with co-existing autoimmune diseases had higher risk of low HDL-C level (OR: 2.96; P < 0.05). CONCLUSIONS: The results have shown significant impact of co-existing autoimmune diseases on lipid profile in patients with T1DM. The most prominent changes were found in HDL lipoprotein characteristics in T1DM + CD group.

Associations of Apgar score and size at birth with lipoprotein subclasses in juvenile obesity

Background/aim: Juvenile obesity is associated with several metabolic abnormalities, one of them being atherogenic dyslipidemia. Suboptimal fetal growth is associated with obesity risk in childhood, but also with increased rate of metabolic diseases in later life. This study investigated associations of neonatal data (Apgar score, birth weight and birth length) with low-density lipoprotein and high-density lipoprotein (LDL and HDL) subclasses in a group of obese children, as well as a possible impact of breastfeeding duration on obesity-associated lipoprotein subclasses distributions.Materials and methods: We included 42 obese children, aged 14.2 ± 2.1 years. LDL and HDL subfractions were separated by gradient gel electrophoresis and biochemical parameters were assessed by routine methods.Results: Compared with obese children with Apgar ≥ 9, the group with Apgar < 9 had significantly higher percentages of small, dense LDL particles (P < 0.05), due to reduced LDL I (P < 0.01) and increased LDL III subclasses (P < 0.05). Birth weight was positively associated with the proportions of LDL I particles (P < 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P < 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P < 0.01) and lower proportion of HDL 2a particles (P < 0.05) than their ≥3 months breastfed peers.Conclusion: The results showed significant associations of neonatal characteristics with LDL and HDL particle distributions in obese children. In addition, our results point toward positive aspects of longer breastfeeding duration on lipoprotein particle distributions in obese children.

Oxidative stress and paraoxonase 1 status in acute ischemic stroke patients.

OBJECTIVE: The connection of oxidative stress with dyslipidemia creates a newly-emerging atherosclerosis risk factor involved in acute ischemic stroke development. This study analyzed the influence of oxidative stress on structural changes of high-density lipoprotein (HDL) particles connected with modification in protective paraoxonase 1 (PON1) activity. METHODS: This study used 185 patients with acute ischemic stroke and 185 apparently healthy controls. Oxidative stress status, PON1 status, lipids and high-sensitivity C-reactive protein (hsCRP) were determined. In isolated HDL lipoprotein fraction we determined selected markers of oxidative stress (malondialdehyde, MDA) and the content of total sulfhydryl (SH) groups. The capability of oxidative and PON1 status parameters to discriminate patients according to survival status was evaluated. RESULTS: Stroke patients had lower HDL-cholesterol than controls and a remarkable fall in PON1 activity (control group-227U/L, survivors-42U/L, lethal outcome group-61U/L, p < 0.001), along with more prominent inflammation. Pronounced oxidative stress and impaired antioxidative protection was present among patients. HDL fraction analysis revealed a significant decrease of SH groups content (control group vs. patients, p < 0.05) and increased in MDA content in patients (lethal outcome vs. control group, p < 0.05). According to logistic regression analysis, the best predictor of disease outcome was oxidative stress marker - prooxidative-antioxidative balance (PAB). CONCLUSIONS: Pronounced oxidative stress in this group of acute ischemic stroke patients probably led to HDL structural changes, which could further cause an alteration or decrease of PON1 activity. Evidence of increased prooxidant level associated with decreased protective, antioxidative factors suggests their mutual involvement in this complex pathology.