Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is a multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed to estimate the connection between relative leucocyte telomere lengths (rLTL) - biomarker of cellular ageing with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both sexes. The results suggested that rLTL are significantly shorter in obese, compared with lean group (P < 0·01). Negative correlation of rLTL with total oxidant status (TOS) (Spearman's ρ = -0·365, P < 0·001) as well as with C-reactive protein (Spearman's ρ = -0·363, P < 0·001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35 % of total variability; antioxidant factor with 30 % of total variability and lipid antioxidant - biological ageing factor with 12 % of the total variability. The most important predictor of BMI > 30 kg/m2 according to logistic regression analysis was PCA-derived antioxidant factor's score (OR: 1·66, 95th Cl 1·05-2·6, P = 0·029). PCA analysis confirmed that oxidative stress importance in biological ageing is caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homoeostasis deepness, even before any overt disease occurrence.

The Effects of Pregestational Overweight and Obesity on Maternal Lipidome in Pregnancy: Implications for Newborns' Characteristics.

Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.

Upregulation of peripheral blood mononuclear cells resistin gene expression in severe obstructive sleep apnea and obstructive sleep apnea with coexisting type 2 diabetes mellitus.

PURPOSE: Obstructive sleep apnea (OSA) is characterised by increased systemic inflammation, and is often accompanied with type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aim of this investigation was to evaluate gene expression of resistin, its receptor CAP1 and CD36 as the indicators of the inflammatory changes in PBMCs in relation to the severity of OSA, and the presence of type 2 diabetes mellitus (T2DM) in OSA. METHODS: Severity of OSA was defined by the apnea/hypopnea index (AHI): AHI < 30: mild to moderate OSA (MM-OSA), AHI ≥ 30: severe OSA (S-OSA). Presence of T2DM was captured: OSA with T2DM (OSA + T2DM), OSA without T2DM (OSA-T2DM). PBMC resistin, CAP1, and CD36 mRNA were determined by real-time PCR. RESULTS: Resistin mRNA was significantly upregulated in S-OSA (N = 54) compared to the MM-OSA (N = 52, P = 0.043); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.302; P = 0.166, respectively). Resistin mRNA was significantly upregulated in OSA + T2DM (N = 29) compared to the OSA-T2DM (N = 77, P = 0.029); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.662; P = 0.108, respectively). AHI and T2DM were independent predictors of resistin mRNA above the 75th percentile (OR = 3.717 [1.152-11.991]; OR = 3.261 [1.000-10.630], P = 0.042 respectively). CONCLUSION: Resistin gene upregulation in S-OSA indicates its possible contribution to increased inflammation in S-OSA and makes it a possible marker of the disease severity. Resistin gene upregulation in OSA + T2DM suggests that a joint effect of these two comorbidities may have a major contribution to increased inflammation and complications that arise from this state.

Cholesterol Metabolic Profiling of HDL in Women with Late-Onset Preeclampsia.

A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and ß-sitosterol) within HDL particles (NCSHDL), the activities of principal modulators of HDL cholesterol's content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (p < 0.05) and followed by lower levels of cholesterol absorption markers (p < 0.001 for campesterolHDL and p < 0.05 for ß-sitosterolHDL). Lowering of HDL cholesterol between trimesters in RG (p < 0.05) was accompanied by a decrease in HDL phytosterol content (p < 0.001), apolipoprotein A-I (apoA-I) concentration (p < 0.05), and paraoxonase 1 (PON1) (p < 0.001), lecithin-cholesterol acyltransferase (LCAT) (p < 0.05), and cholesterol ester transfer protein (CETP) activities (p < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCSHDL in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol.

Non-Coding RNAs in Preeclampsia-Molecular Mechanisms and Diagnostic Potential.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Defects in trophoblast invasion, differentiation of extravillous trophoblasts and spiral artery remodeling are key factors in PE development. Currently there are no predictive biomarkers clinically available for PE. Recent technological advancements empowered transcriptome exploration and led to the discovery of numerous non-coding RNA species of which microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most investigated. They are implicated in the regulation of numerous cellular functions, and as such are being extensively explored as potential biomarkers for various diseases. Altered expression of numerous lncRNAs and miRNAs in placenta has been related to pathophysiological processes that occur in preeclampsia. In the following text we offer summary of the latest knowledge of the molecular mechanism by which lnRNAs and miRNAs (focusing on the chromosome 19 miRNA cluster (C19MC)) contribute to pathophysiology of PE development and their potential utility as biomarkers of PE, with special focus on sample selection and techniques for the quantification of lncRNAs and miRNAs in maternal circulation.

The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet.

CONTEXT: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. OBJECTIVES: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. MATERIALS AND METHODS: Eighteen male Wistar albino rats were divided into three groups (n = 6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. RESULTS: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p = 0.021 for HO-1 [0.85 (0.61-3.45)], p = 0.047 for MCP-1 and [176.5 (66.50-221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p = 0.049]. CONCLUSIONS: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.

Association of adenylate cyclase-associated protein 1 with coronary artery disease.

BACKGROUND: Adenylate cyclase-associated protein 1 (CAP1) is a recently identified receptor for human resistin. As resistin has been related to CAD development and progression and CAP1 has never been evaluated in CAD, the aim of this study was to determine its peripheral blood mononuclear cells (PBMCs) mRNA in patients with CAD, and resistin plasma concentration, PBMCs resistin and CD36 mRNA, considering resistiǹs ability to stimulate CD36 expression in vitro. MATERIALS AND METHODS: This case-controlled study included 27 healthy subjects (CG) and 66 patients requiring coronary angiography. Of the latter, 42 had nonsignificant CAD whereas 24 had significant CAD. Circulating resistin was measured by ELISA; PBMCs CAP1, resistin and CD36 mRNA were determined by real-time PCR. RESULTS: Patients with significant as well as patients with nonsignificant CAD had significantly higher resistin concentrations compared to the CG (P < 0·001; P = 0·003). Resistin mRNA did not show significant difference between the investigated groups. CAP1 and CD36 mRNA were significantly higher in significant CAD (P < 0·001; P < 0·001, respectively) and nonsignificant CAD (P < 0·001; P < 0·001, respectively) compared to the CG; significant CAD showed significantly higher CD36 mRNA (P = 0·040) compared to the nonsignificant CAD group. Multiple linear regression analysis identified Tg and CD36 mRNA as independent predictors of CAP1 (R2  = 0·402; adjR2  = 0·376). CONCLUSION: Significant up-regulation of PBMCs CAP1, CD36 mRNA and plasma resistin found in significant CAD, as well as in nonsignificant CAD compared to CG, indicates that resistin could be able to exert its effects stronger on cells with up-regulated CAP1 mRNA thus contributing atherosclerosis development.

Expression analysis of microRNAs and cytokine mRNAs in pregnancies complicated by gestational hypertension.

OBJECTIVES: Gestational hypertension (GH1) is one of the most common pregnancy-related complications, however, there is still insufficient knowledge about its development and molecular changes. The aim of our study was to examine the expression of miR-17, miR-29a and miR-181a, as well as TNF-α, IL-1ß, IL-6 and IL-17 in women with GH and to investigate possible correlations between these parameters. STUDY DESIGN: The study included 64 pregnant women, placed either in the control or the GH group. Quantitative real-time PCR (qPCR2) was used to determine expression levels of microRNAs and cytokines' mRNAs. MAIN OUTCOME MEASURES: Expression levels of miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines mRNAs (TNF-α, IL-1ß, IL-6 and IL-17) in women with gestational hypertension were compared to the control group (healthy pregnant women). RESULTS: No significant changes in microRNAs expression level were found between compared groups. TNF-α was significantly upregulated in the GH group compared to controls. Expression levels of other investigated cytokines did not differ between examined groups. ROC curve analysis indicated that TNF-α does not show sufficient ability to discriminate between CG and GH patients. TNF-α was significantly positively correlated with IL-1ß and IL-17 and negatively correlated with miR-181a. CONCLUSIONS: Our results point to the involvement of proinflamatory cytokines in gestational hypertension. Although increased expression of TNF-α was found in the GH group, this cytokine did not show sufficient ability to discriminate between GH and healthy pregnancies.

Targeting noncoding RNAs to treat atherosclerosis.

Noncoding RNAs (ncRNAs) are pivotal for various pathological processes, impacting disease progression. The potential for leveraging ncRNAs to prevent or treat atherosclerosis and associated cardiovascular diseases is of great significance, especially given the increasing prevalence of atherosclerosis in an ageing and sedentary population. Together, these diseases impose a substantial socio-economic burden, demanding innovative therapeutic solutions. This review explores the potential of ncRNAs in atherosclerosis treatment. We commence by examining approaches for identifying and characterizing atherosclerosis-associated ncRNAs. We then delve into the functional aspects of ncRNAs in atherosclerosis development and progression. Additionally, we review current RNA and RNA-targeting molecules in development or under approval for clinical use, offering insights into their pharmacological potential. The importance of improved ncRNA delivery strategies is highlighted. Finally, we suggest avenues for advanced research to accelerate the use of ncRNAs in treating atherosclerosis and mitigating its societal impact.

Expression of miRNAs and proinflammatory cytokines in pregnant women with gestational diabetes mellitus.

Altered microRNAs (miRNAs1) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM2), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR3). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1ß were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1ß had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1ß and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1ß making them markers of this condition.

LncRNAs as Regulators of Atherosclerotic Plaque Stability.

Current clinical data show that, despite constant efforts to develop novel therapies and clinical approaches, atherosclerotic cardiovascular diseases (ASCVD) are still one of the leading causes of death worldwide. Advanced and unstable atherosclerotic plaques most often trigger acute coronary events that can lead to fatal outcomes. However, despite the fact that different plaque phenotypes may require different treatments, current approaches to prognosis, diagnosis, and classification of acute coronary syndrome do not consider the diversity of plaque phenotypes. Long non-coding RNAs (lncRNAs) represent an important class of molecules that are implicated in epigenetic control of numerous cellular processes. Here we review the latest knowledge about lncRNAs' influence on plaque development and stability through regulation of immune response, lipid metabolism, extracellular matrix remodelling, endothelial cell function, and vascular smooth muscle function, with special emphasis on pro-atherogenic and anti-atherogenic lncRNA functions. In addition, we present current challenges in the research of lncRNAs' role in atherosclerosis and translation of the findings from animal models to humans. Finally, we present the directions for future lncRNA-oriented research, which may ultimately result in patient-oriented therapeutic strategies for ASCVD.

The Prospect of Genomic, Transcriptomic, Epigenetic and Metabolomic Biomarkers for The Personalized Prevention of Type 2 Diabetes and Cardiovascular Diseases.

Cardiometabolic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular disease (CVD), are a great health concern. The strategies aimed to increase awareness and prevention, in conjunction with timely diagnosis and optimal management of these conditions, represent the main lines of action to improve life expectancy and quality. In recent years, the introduction of innovative therapies for the treatment of DM and CVD has provided new hope for high-risk patients. Yet, the implementation of preventive measures in achieving cardiometabolic health is far from successful and requires further improvement. The development of cardiometabolic disorders is a complex, multifactorial process involving several metabolic pathways as well as genetic and environmental factors. Decreasing cumulative exposure during the entire life course and timely recognition and targeting of potential riskenhancing factors could pave the way toward more successful prevention of cardiometabolic disorders. Nowadays, in the era of "omics" technologies, it is possible to identify novel biomarkers and therapeutic targets, which offers the possibility to apply an individualized approach for each patient. This review will discuss potential applications of genomic, transcriptomic, epigenetic and metabolomic biomarkers for the personalized prevention of cardiometabolic diseases.

Micro-ribonucleic acid modulation with oxidative stress and inflammation in patients with type 2 diabetes mellitus - a review article.

In parallel with the rapid growth of obesity, there is also an increase in the prevalence of type 2 diabetes mellitus (T2D) worldwide. Due to its complications, cardiovascular diseases are the leading cause of death in those patients. In the last two decades, special attention has been given to oxidative stress and inflammation, as the underlying mechanisms related to T2D occurrence and progression. Moreover, micro-ribonucleic acids (miRNAs) as new genetic biomarkers take an important place in the investigation of different metabolic pathways of insulin signaling. In this review article, we discuss microRNA modulation with oxidative stress and inflammation in patients with T2D. Better insight into the novel potential therapeutic targets for treatment of diabetes and its complications is of utmost importance for public health.

Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus.

Background: Type 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autoreactivity toward b-cells is controlled by significant changes in metabolism of T cells. Mammalian target of rapamycin (mTOR) is an important intracellular regulator of metabolism and cell growth. MAPK/MAK/MRK overlapping kinase 1 (MOK1) is one of the less known regulators of mTOR. We sought to investigate if MOK1 and mTOR mRNA levels in peripheral blood mononuclear cells (PBMCs) of T1DM pediatric patients are different compared to healthy subjects. Methods: This study included 172 adolescents with T1DM and 36 healthy adolescent volunteers designated for control group (CG). MOK1 and mTOR mRNA levels were determined in PBMCs by qPCR. Results: T1DM patients have significant downregulation of MOK1 mRNA levels in PBMCs compared CG (P=0.018), while there was no significant difference in mTOR mRNA levels (P=0.891). Furthermore, in T1DM patients, MOK1 significantly correlated with age, triglycerides and mTOR, while mTOR correlated significantly with BMI and systolic blood pressure. Overweight T1DM subjects had significantly lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA levels, together with significantly higher levels of systolic blood pressure (P<0.001), total cholesterol (P=0.001), LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi - variate analysis showed that MOK1 was independently negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175-0.997), p=0.049). Conclusions: Our study demonstrated for the first time that T1DM is associated with MOK1 downregulation. In addition, downregulation of both mTOR and MOK1 gene expressions was associated with cardiovascular risk factors in overweight T1DM patients.

Transforming Growth Factor-ß1 and Receptor for Advanced Glycation End Products Gene Expression and Protein Levels in Adolescents with Type 1 iabetes Mellitus

Objective: Type 1 diabetes (T1D) mellitus is one of the most frequent autoimmune diseases in childhood. Chronic complications are the main causes of cardiovascular morbidity and mortality in T1D. Although interactions between advanced glycation end products (AGE) and their receptors (RAGE) and transforming growth factor-ß1 (TGF-ß1) are implicated in development and progression of diabetic microand macro-vascular complications, they also have important roles in immune system regulation. Methods: Blood samples were obtained from 156 adolescents with T1D and 80 apparently healthy controls. T1D patients diagnosed with any other autoimmune disease and receiving any kind of drugs except insulin therapy were excluded from this study. Exclusion criteria for controls were positive family history of T1D and drugs/supplements application. TGF-ß1 and transmembrane full-length RAGE (flRAGE) messenger ribonucleic acid (mRNA) levels in peripheral blood mononuclear cells (PBMC) were obtained by quantitative polymerase chain reaction (qPCR) method. Circulating levels of biochemical markers, TGF-ß1 and soluble RAGE (sRAGE) levels were also determined. Results: TGF-ß1 and flRAGE mRNA levels were significantly higher in controls compared to patients (p<0.001, for both). However, TGF-ß1 and sRAGE levels were higher in patients than controls (p<0.001, for both). There were significant independent associations of all mRNA and protein levels with T1D. TGF-ß1 mRNA was the only marker independently negatively associated with urinary albumin excretion rate in T1D adolescents (p=0.005). Conclusion: Our results indicated gene expression downregulation of TGF-ß1 and flRAGE in PBMC of T1D adolescents. TGF-ß1 mRNA downregulation may be useful for predicting early elevation of urinary albumin excretion rate.

Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in Serbian population.

BACKGROUND: Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. METHODS: The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. RESULTS: Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). CONCLUSIONS: This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls.

BACKGROUND: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. AIMS: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. METHODS: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. RESULTS: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). CONCLUSION: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

Paraoxonase 1 and atherosclerosis-related diseases.

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.

Superoxide Dismutase Isoenzymes Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Coronary Artery Disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association Between Superoxide Dismutase Isoenzyme Gene Expression and Total Antioxidant Status in Patients with an End-Stage Renal Disease

Background: Chronic renal failure, particularly end-stage renal disease, is a serious health problem associated with a high mortality rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Aims: To examine superoxide dismutase isoenzyme gene expression in peripheral blood mononuclear cells of patients on hemodialysis and to determine the associations between superoxide dismutase isoenzyme gene expression, oxidative stress, and non-enzymatic antioxidative protection. Study Design: Case control study. Methods: This study included 33 patients on hemodialysis (age, 55.33±15.31 years old) and 33 apparently healthy controls (age, 45.37±8.92 years old). Superoxide dismutase isoenzyme messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. General biochemical parameters, high sensitivity C-reactive protein, total antioxidant status, thiobarbituric acid-reactive substances, and the superoxide anion radical were also determined. Results: Normalized Cu/Zn superoxide dismutase and Mn superoxide dismutase messenger ribonucleic acid levels were significantly higher in patients than controls (p<0.001 and p=0.011). A significant negative correlation was detected between normalized Cu/Zn superoxide dismutase messenger ribonucleic acid levels and total protein, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total antioxidant status. Normalized Mn superoxide dismutase messenger ribonucleic acid levels were negatively correlated with total protein and total antioxidant status. A multiple regression analysis revealed independent associations between total antioxidant status and normalized Cu/Zn superoxide dismutase (p=0.038) and between total antioxidant status and normalized Mn superoxide dismutase messenger ribonucleic acid levels (p=0.038 and p=0.018, respectively). Conclusion: The superoxide dismutase isoenzyme gene is expressed at a higher rate in patients with end-stage renal failure, probably due to increased oxidative stress and attenuated antioxidative defense. The plasma total antioxidant status is an independent predictor of normalized superoxide dismutase isoenzyme messenger ribonucleic acid levels.