Sphingosine 1-Phosphate and Apolipoprotein M Levels and Their Correlations with Inflammatory Biomarkers in Patients with Untreated Familial Hypercholesterolemia.

High-density lipoprotein (HDL)-bound apolipoprotein M/sphingosine 1-phosphate (ApoM/S1P) complex in cardiovascular diseases serves as a bridge between HDL and endothelial cells, maintaining a healthy endothelial barrier. To date, S1P and ApoM in patients with untreated heterozygous familial hypercholesterolemia (HeFH) have not been extensively studied. Eighty-one untreated patients with HeFH and 32 healthy control subjects were included in this study. Serum S1P, ApoM, sCD40L, sICAM-1, sVCAM-1, oxLDL, and TNFα concentrations were determined by ELISA. PON1 activities were measured spectrophotometrically. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Significantly higher serum S1P and ApoM levels were found in HeFH patients compared to controls. S1P negatively correlated with large HDL and positively with small HDL subfractions in HeFH patients and the whole study population. S1P showed significant positive correlations with sCD40L and MMP-9 levels and PON1 arylesterase activity, while we found significant negative correlation between sVCAM-1 and S1P in HeFH patients. A backward stepwise multiple regression analysis showed that the best predictors of serum S1P were large HDL subfraction and arylesterase activity. Higher S1P and ApoM levels and their correlations with HDL subfractions and inflammatory markers in HeFH patients implied their possible role in endothelial protection.

Determination of Serum Progranulin in Patients with Untreated Familial Hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated LDL-C concentrations and is associated with an increased risk of premature atherosclerosis. Progranulin (PGRN) is a multifunctional protein that is known to have various anti-atherogenic effects. To date, the use of serum PGRN in patients with FH has not been studied. METHODS: In total, 81 untreated patients with heterozygous FH (HeFH) and 32 healthy control subjects were included in this study. Serum PGRN, sICAM-1, sVCAM-1, oxLDL and TNFα concentrations were determined by ELISA. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. RESULTS: We could not find a significant difference between the PGRN concentrations of the HeFH patients and controls (37.66 ± 9.75 vs. 38.43 ± 7.74 ng/mL, ns.). We found significant positive correlations between triglyceride, TNFα, sVCAM-1, the ratio of small HDL subfraction and PGRN, while significant negative correlations were found between the ratio of large HDL subfraction and PGRN both in the whole study population and in FH patients. PGRN was predicted by sVCAM-1, logTNFα and the ratio of small HDL subfraction. CONCLUSIONS: The strong correlations between HDL subfractions, inflammatory markers and PGRN suggest that PGRN may exert its anti-atherogenic effect in HeFH through the alteration of HDL composition and the amelioration of inflammation rather than through decreasing oxidative stress.

Determining the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods in the Northeastern region of Hungary.

Objective: Identifying hypertension in children and providing treatment for it have a marked impact on the patients' long-term cardiovascular outcomes. The global prevalence of childhood hypertension is increasing, yet its investigation has been rather sporadic in Eastern Europe. Therefore, our goal was to determine the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods. Methods: We evaluated data from 3 to 18-year-old children who visited the University of Debrecen Clinical Center's hospital throughout a 15-year study period (n = 92,198; boys/girls: 48/52%). Results: We identified a total of 3,687 children with hypertension (2,107 boys and 1,580 girls), with a 4% calculated prevalence of hypertension in the whole study population and a higher prevalence in boys (4.7%) as compared to girls (3.2%). Among boys we found an increasing prevalence in consecutive age groups in the study population, but among girls the highest prevalences are identified in the 12-15-year age group. Markedly higher BMI values were found in hypertensive children as compared to non-hypertensives in all age groups. Moreover, significantly higher total cholesterol (4.27 ± 0.95 vs. 4.17 ± 0.88 mmol/L), LDL-C (2.62 ± 0.79 vs. 2.44 ± 0.74 mmol/L) and triglyceride (1.2 (0.85-1.69) vs. 0.94 (0.7-1.33) mmol/L), and lower HDL-C (1.2 ± 0.3 vs. 1.42 ± 0.39 mmol/L) levels were found in hypertensive children. Furthermore, significantly higher serum uric acid levels were found in children with hypertension (299.2 ± 86.1 vs. 259.9 ± 73.3 µmol/L), while glucose levels did not differ significantly. Conclusion: Our data suggest that the calculated prevalence of childhood hypertension in our region is comparable to data from other European countries and is associated with early metabolic disturbances. Data mining is an effective method for identifying childhood hypertension and its metabolic consequences.

Effects of alpha-lipoic acid treatment on serum progranulin levels and inflammatory markers in diabetic neuropathy.

OBJECTIVES: Progranulin (PGRN) is a secreted growth factor that helps to regulate neuronal survival by blocking tumor necrosis factor-alpha (TNFα) receptors. The antioxidant alpha-lipoic acid (ALA) is used in diabetic neuropathy to improve nerve conduction and relieve neuropathic pain, but its effects on PGRN levels have not yet been elucidated. METHODS: In this prospective study, 54 patients with type 2 diabetes and peripheral neuropathy received 600 mg of ALA daily for 6 months. Twenty-four patients with diabetes without neuropathy were also included in the study. Serum PGRN and TNFα levels were determined using enzyme-linked immunosorbent assays. In addition, current perception threshold (CPT) testing was used to assess sensory neuropathy. RESULTS: After ALA treatment, serum PGRN levels were significantly increased and CPT values were significantly improved. Furthermore, there were significant positive correlations among TNFα, ICAM-1, and PGRN levels both before and after ALA treatment. A significant negative correlation was observed between the improvements in CPT and the PGRN levels. Furthermore, ICAM-1 levels were an independent predictor of PGRN levels. CONCLUSIONS: Changes in serum PGRN levels indicate that ALA treatment may have beneficial effects on endothelial function and neuronal inflammation.

[Diagnostic and prognostic roles of serum progranulin, a novel marker of the carbohydrate metabolism and inflammation]. / A szénhidrát-anyagcsere és a gyulladásos folyamatok jellemzésére szolgáló új marker, a szérumprogranulin diagnosztikai és prognosztikai szerepérol.

Progranulin is a recently recognized multifunctional glycopeptide shown to be related to obesity and diabetes mellitus. Progranulin is an endogenous antagonist of tumor necrosis factor-α by competitively binding to its receptor, therefore, it exerts anti-inflammatory activity. Paradoxically, previous studies have shown that serum levels of progranulin were elevated in patients with diabetes and associated to its complications including micro- and macroangiopathies, macroalbuminuria or reduced renal function. Moreover, hyperprogranulinemia may be involved in the pathogenesis of obesity-associated insulin resistance. The review summarizes the currently available data on progranulin as a novel marker of the carbohydrate metabolism and inflammation. Orv Hetil. 2019; 160(25): 973-979.

[The role of apolipoprotein M and sphingosine 1-phosphate axis in the prevention of atherosclerosis]. / Az apolipoprotein M és a szfingozin-1-foszfát tengely jelentosége az érelmeszesedés kialakulásának gátlásában.

Previous studies showed that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to risk of cardiovascular diseases. However, in the last few decades it became obvious that beyond its plasma level, HDL structure and function have a critical role in its anti-atherogenic efficacy. Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL metabolism and exhibits various anti-atherosclerotic functions, such as protection against oxidation and regulation of cholesterol efflux. Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that regulates numerous cellular responses including cell differentiation and migration, apoptosis and vascular inflammation. The majority of S1P is associated to ApoM containing HDL particles. Therefore, ApoM and S1P content of HDL have an impact on the atherosclerotic process. Moreover, HDL-ApoM and S1P content can be altered in several pathologic conditions such as coronary artery disease. This review covers the currently available data on the contribution of ApoM and S1P to HDL function in health and cardiovascular diseases. Orv Hetil. 2018; 159(5): 168-175.