Effects of monacolin K-containing nutraceutical on cholesterol homeostasis re-establishment and CVD risk reduction in hypercholesterolemic subjects.

OBJECTIVE: Hypercholesterolemia is caused by cholesterol homeostasis (CH) disruption, and it contributes to cardiovascular diseases pathogenesis and progression. Status of CH can be assessed by measuring serum concentrations of non-cholesterol sterols (NCS) which serve as cholesterol synthesis and absorption surrogate markers. Monacolin K, isolated from red yeast rice, influences cholesterol synthesis by inhibiting HMG-CoA reductase activity and reduces serum total cholesterol (TC) concentration. PATIENTS AND METHODS: This longitudinal study included 30 hypercholesterolemic patients, with systematic coronary risk estimation (SCORE) values <10%, who received 3-months-long supplementation with nutraceutical mixture containing monacolin K, and vitamins C, B1 and K2. Serum NCS were quantified by HPLC-MS/MS method. Atherogenic indexes were calculated from lipid status parameters concentrations. Albumin degradation inhibition test was conducted to estimate in vitro anti-inflammatory activity of the nutraceutical mixture, whereas in vitro antioxidant activity was measured in serum enriched with prooxidants and antioxidants. RESULTS: TC, LDL-cholesterol (LDL-C), and triglycerides (TG) concentrations (p<0.001), as well as atherogenic indexes and SCORE values (p<0.001, p<0.01, respectively) were lowered following the supplementation. Concentrations of cholesterol synthesis markers were decreased (p<0.001), whereas levels of cholesterol absorption markers remained unchanged after the supplementation. Reduction in cholesterol synthesis went alongside reductions in lipid status parameters and atherogenic indexes. In vitro analyses showed certain anti-inflammatory and antioxidant activity of the nutraceutical. CONCLUSIONS: These results suggest that supplementation with monacolin K containing nutraceutical favorably influences lipid status parameters and atherogenic indexes by acting on cholesterol synthesis. Anti-inflammatory and antioxidant effects of this unique nutraceutical mixture may exhibit beneficial pleiotropic effects.

Potential use of serum insulin-like growth factor 1 and E-cadherin as biomarkers of colorectal cancer.

AIM: Despite many efforts, reliable biomarkers for the prediction and diagnosis of colorectal cancer (CRC) are still missing. Insulin-like growth factor 1 (IGF-1) and E-cadherin are recognized as potential biomarkers, but their diagnostic capacity is largely unexplored in CRC. The aim of this work is to investigate IGF-1 and E-cadherin levels with respect to various characteristics of CRC and to estimate their diagnostic potential. METHOD: Seventy CRC patients and 75 healthy individuals were enrolled. IGF-1 and E-cadherin were determined using enzyme-linked immunosorbent assay. The predictive and diagnostic capacities of IGF-1 and E-cadherin were estimated by logistic regression analysis and by determination of the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Concentrations of IGF-1 were lower (P = 0.019) while levels of E-cadherin were higher (P < 0.001) in CRC patients than in controls. IGF-1 concentration decreased in parallel with age and progression of CRC (P = 0.023). Also, IGF-1 was higher in men with CRC than in women (P = 0.003). E-cadherin levels were unaffected by variations in either anthropometric characteristics of CRC patients, or localization, grade and stage of the tumour. Both IGF-1 and E-cadherin were independently associated with CRC (P = 0.040; P < 0.001, respectively). The diagnostic accuracy of IGF-1 was estimated as acceptable (AUC = 0.757; P < 0.001), while the diagnostic accuracy of E-cadherin was outstanding (AUC = 0.954; P < 0.001). CONCLUSIONS: Decreased IGF-1 and increased E-cadherin levels were found in CRC patients. IGF-1, but not E-cadherin, concentrations differed according to age, gender and stage of CRC. Both markers were independently associated with the presence of the disease, while E-cadherin demonstrated high diagnostic accuracy.

Inverse association between serum endocan levels and small LDL and HDL particles in patients with type 2 diabetes mellitus.

OBJECTIVE: Determination of lipoprotein size and subclasses distribution can provide more significant information on cardiovascular disease risk than measurement of traditional lipid parameters alone. Accordingly, we aimed to examine their potential relationship with the novel biomarker of endothelial dysfunction, such as endocan in patients with type 2 diabetes mellitus (T2D), since there are no studies concerning this issue. PATIENTS AND METHODS: This case-control study included a total of 42 individuals with T2D and 64 diabetes-free participants. Serum endocan, lipid parameters, and lipoprotein subclasses were measured. RESULTS: Patients with T2D exhibited higher proportion of the smallest high-density lipoprotein (HDL) particles HDL 3c, as compared with diabetes-free participants (p=0.047). Higher serum endocan levels in T2D patients with low small dense low-density lipoprotein (LDL) particles (sdLDL) %, as compared with corresponding group of diabetes-free subjects was shown (p<0.01). Univariate binary logistic analysis revealed significant positive association of endocan and LDL diameter (OR=1.686, p=0.004), and negative associations of endocan with proportions of sdLDL (OR=0.928, p=0.007) and HDL3b (OR=0.789, p=0.009) particles. In a multivariate analysis, LDL diameter and proportions of sdLDL and HDL3b subclasses remained independent predictors of endocan levels in tested population. CONCLUSIONS: The results of our study showed that larger LDL diameters, but lower sdLDL and HDL3b proportions were associated with higher endocan levels in population with T2D. More studies in the future are needed to confirm the observed relationship and to examine its causal nature.

Association of oxidative stress and PON1 with LDL and HDL particle size in middle-aged subjects.

BACKGROUND: Alterations in plasma lipoprotein subclass distributions affect atherosclerosis risk. Smaller, denser low-density lipoprotein (LDL) particles (sdLDL) are more susceptible to oxidation. In contrast, most of the protective effects of high-density lipoproteins (HDL) are attributable to larger particles. This study investigates the connection between LDL and HDL particle heterogeneity and oxidative stress, antioxidative defence (AOD) and paraoxonase (PON1) status in a healthy middle-aged Serbian population. MATERIALS AND METHODS: LDL and HDL particle sizes and subclass distributions were measured by gradient gel electrophoresis in 104 men and 103 women, aged 53 +/- 9.4 years. PON1 activities and PON1(Q192R) phenotypes were determined with paraoxon and diazoxon as substrates. The oxidative stress/AOD status was estimated by measuring malondialdehyde (MDA) and superoxide-anion (O2*(-)) levels and superoxide-dismutase (SOD) activity. RESULTS: Subjects with sdLDL had significantly higher MDA (P < 0.001) and O2*(-)(P < 0.05) levels and greater diazoxonase (DZOase) activity (P < 0.05) compared to subjects with larger LDL particles. A high MDA concentration was a significant predictor of the sdLDL phenotype (P < 0.005). Increased levels of and MDA were associated with smaller HDL(3) subclass abundance. Reduced HDL particle size was associated with lower DZOase activity (P < 0.01). CONCLUSIONS: Even in the absence of symptoms of atherosclerosis, sdLDL particles are associated with increased oxidative stress, which may stimulate a compensatory rise in PON1 DZOase activity. Elevated oxidative stress may significantly affect HDL subclass distribution, resulting in the accumulation of smaller, denser HDL particles with diminished antioxidative capacity.