Noémi Zsíros

Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications.

OBJECTIVES Myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were shown to contribute to atherogenesis, while human paraoxonase-1 (PON1) protects against oxidative stress. Although several studies investigated these biomarkers, their associations have not been completely clarified yet. We aimed to investigate these parameters in overweight hyperlipidemic, lipid-lowering therapy-naive patients (n=167) with and without vascular complications. DESIGN AND METHODS MPO, MMP-9 and TIMP-1 levels were measured by ELISA. PON1 activities were detected spectrophotometrically. PON1 phenotype was calculated by using a dual substrate method. RESULTS Patients with vascular complications (VC) had significantly higher MPO and TIMP-1 levels compared to those without (patients with no vascular complications; NVC) (728 (367.25-1177.90) mg/ml vs. 315.9 (176.05-687.40) mg/ml; p<0.001; and 172.7 (157.7-197.7) ng/ml vs. 152.6 (129.3-172.3) ng/ml; p<0.0001; respectively). MPO levels showed a significant negative correlation with PON1 arylesterase activity (whole patient group (W): r=0.42, p<0.0001; VC: r=0.44, p=0.01; NVC: r=0.39, p<0.0001) and positive correlations with MMP-9 (W: r=0.37, p<0.0001; VC: r=0.29, p=0.07; NVC: r=0.42, p<0.0001) and TIMP-1 (W: r=0.42, p<0.0001; VC: r=0.33, p<0.05; NVC: r=0.41, p<0.0001), respectively. PON1 arylesterase activity was found to be an independent predictor of MPO levels in the whole patient group (β=-0.350, p<0.0001) or when studied separately in the subgroups with or without cardiovascular complications (VC: β=-0.57, p<0.05; NVC: β=-0.33, p<0.0001). CONCLUSIONS Our results suggest that parallel investigation of MPO, MMP-9 and TIMP-1 levels and PON1 arylesterase activity may be a more accurate indicator of atherosclerosis, which may allow earlier treatment and therefore, improvement of treatment efficacy.

Estimating the predictive validity of diabetic animal models in rosiglitazone studies.

For therapeutic studies, predictive validity of animal models – arguably the most important feature of animal models in terms of human relevance – can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species‐based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals.

Az emelkedett lipoprotein(a)-szint klinikai jelentosége és kezelési lehetoségei

Lipoprotein(a) has been shown to be associated with an increased incidence of cardiovascular diseases for decades. However, only recent research revealed more about its physiological function and its role in the development of cardiovascular diseases. The authors summarize the physiological role of lipoprotein(a), causes and treatment of elevated lipoprotein(a) level, and the association between lipoprotein(a) and cardiovascular diseases.

Clinical significance of and treatment options for increased lipoprotein(a)

Lipoprotein(a) has been shown to be associated with an increased incidence of cardiovascular diseases for decades. However, only recent research revealed more about its physiological function and its role in the development of cardiovascular diseases. The authors summarize the physiological role of lipoprotein(a), causes and treatment of elevated lipoprotein(a) level, and the association between lipoprotein(a) and cardiovascular diseases.

Clinical significance and treatment options of increased lipoprotein(a)

Lipoprotein(a) has been shown to be associated with an increased incidence of cardiovascular diseases for decades. However, only recent research revealed more about its physiological function and its role in the development of cardiovascular diseases. The authors summarize the physiological role of lipoprotein(a), causes and treatment of elevated lipoprotein(a) level, and the association between lipoprotein(a) and cardiovascular diseases.

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

BACKGROUND In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. PATIENTS AND METHODS Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. RESULTS We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. CONCLUSIONS It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

Az emelkedett lipoprotein(a)-szint klinikai jelentősége és kezelési lehetőségei@@@Clinical significance and treatment options of increased lipoprotein(a)

Lipoprotein(a) has been shown to be associated with an increased incidence of cardiovascular diseases for decades. However, only recent research revealed more about its physiological function and its role in the development of cardiovascular diseases. The authors summarize the physiological role of lipoprotein(a), causes and treatment of elevated lipoprotein(a) level, and the association between lipoprotein(a) and cardiovascular diseases.

Statin-induced adverse effects – facts and genes

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients.