Browsing by Author "Gojković, Tamara (55191372700)"

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM. © 2022 by the authors.

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM. © 2022 by the authors.

Recent invitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P=0.031) and PBMCs resistin mRNA (P=0.004) were significantly higher in patients with proportion of sdLDL particles ≥50%, compared to the group with relative proportion of sdLDL particles <50%. Plasma resistin correlated positively with creatinine (r=0.456, P<0.001) and resistin mRNA (r=0.298, P=0.014) but negatively with body mass index (r=-0.254, P=0.034) and total cholesterol (r=-0.286, P=0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R2=0.258; adjR2=0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype. © 2016 John Wiley & Sons Australia, Ltd.

Recent invitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P=0.031) and PBMCs resistin mRNA (P=0.004) were significantly higher in patients with proportion of sdLDL particles ≥50%, compared to the group with relative proportion of sdLDL particles <50%. Plasma resistin correlated positively with creatinine (r=0.456, P<0.001) and resistin mRNA (r=0.298, P=0.014) but negatively with body mass index (r=-0.254, P=0.034) and total cholesterol (r=-0.286, P=0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R2=0.258; adjR2=0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype. © 2016 John Wiley & Sons Australia, Ltd.

Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved. Materials and methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and β-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). β-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/β-sitosterol (P < 0.001) and 7-DHC/β-sitosterol (P = 0.005) ratios significantly declined during disease remission. Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission. © by Croatian Society of Medical Biochemistry and Laboratory Medicine.

Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved. Materials and methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and β-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). β-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/β-sitosterol (P < 0.001) and 7-DHC/β-sitosterol (P = 0.005) ratios significantly declined during disease remission. Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission. © by Croatian Society of Medical Biochemistry and Laboratory Medicine.

Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients. This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction. Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p<0.001) and TAS (p<0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p<0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p<0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034). Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood. © 2019 Ana Ninić, Nataša Bogavac-Stanojević, Miron Sopić, Jelena Munjas, Jelena Kotur-Stevuljević, Milica Miljković, Tamara Gojković, Dimitra Kalimanovska-Oštrić, Vesna Spasojević-Kalimanovska.

Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients. This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction. Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p<0.001) and TAS (p<0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p<0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p<0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034). Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood. © 2019 Ana Ninić, Nataša Bogavac-Stanojević, Miron Sopić, Jelena Munjas, Jelena Kotur-Stevuljević, Milica Miljković, Tamara Gojković, Dimitra Kalimanovska-Oštrić, Vesna Spasojević-Kalimanovska.