Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1

2004 ◽  
Vol 107 (5) ◽  
pp. 435-447 ◽  
Author(s):  
Sara P. DEAKIN ◽  
Richard W. JAMES
Keyword(s):  
Environmental Factors ◽  
Serum Concentration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Human Populations ◽  
Genetic And Environmental Factors ◽  
Oxidatively Modified

PON1 (paraoxonase-1) is an HDL (high-density lipoprotein)-associated enzyme capable of hydrolysing diverse substrates from OP (organophosphate) toxins to oxidized phospholipids. As such, it has been linked with both the prevention of OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified LDL (low-density lipoprotein). Mice deficient in PON1 are more susceptible to OP poisoning and oxidative stress and more prone to develop atherosclerosis than their wild-type siblings. There are a number of polymorphisms in the PON1 gene which affect serum PON1 activity and concentration. Many (but not all) studies in human populations have suggested that these polymorphisms may be a risk factor for atherosclerosis. The serum concentration of PON1 across the general population is highly variable and there is some debate as to whether genotype or phenotype (i.e. the quantity or quality of the enzyme) is most accurately associated with risk of disease development. What is clear is that factors influencing serum levels of PON1, be they genetic or environmental, will, in turn, affect the capacity of HDL to protect LDL from oxidation and, consequently, may be linked to atherosclerosis. This review will focus on mechanisms which determine the serum concentration of PON1, including gene expression and genetic polymorphisms, protein secretion and association with HDL, pharmacological and environmental factors.

scholarly journals Potential Cardiovascular Risk Protection of Bilirubin in End-Stage Renal Disease Patients under Hemodialysis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maria do Sameiro-Faria ◽  
Michaela Kohlova ◽  
Sandra Ribeiro ◽  
Petronila Rocha-Pereira ◽  
Laetitia Teixeira ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Paraoxonase 1 ◽  
Low Density ◽  
Genotype Distribution ◽  
Apo B ◽  
Risk Protection

We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. TheUGT1A1genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found inUGT1A1genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients.

scholarly journals Distribution of Paraoxonase-1 (PON-1) and Lipoprotein Phospholipase A2 (Lp-PLA2) across Lipoprotein Subclasses in Subjects with Type 2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Angelina Passaro ◽  
Giovanni Battista Vigna ◽  
Arianna Romani ◽  
Juana M. Sanz ◽  
Carlotta Cavicchio ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Protective Role ◽  
Lipoprotein Cholesterol ◽  
Paraoxonase 1 ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein Subclasses

Paraoxonase-1 (PON1) and lipoprotein phospholipase A2 (Lp-PLA2) may exert an important protective role by preventing the oxidative transformation of high- and low-density lipoproteins (HDL and LDL, respectively). The activity of both enzymes is influenced by lipidome and proteome of the lipoprotein carriers. T2DM typically presents significant changes in the molecular composition of the lipoprotein subclasses. Thus, it becomes relevant to understand the interaction of PON1 and Lp-PLA2 with the subspecies of HDL, LDL, and other lipoproteins in T2DM. Serum levels of PON1-arylesterase and PON1-lactonase and Lp-PLA2 activities and lipoprotein subclasses were measured in 202 nondiabetic subjects (controls) and 92 T2DM outpatients. Arylesterase, but not lactonase or Lp-PLA2 activities, was inversely associated with TD2M after adjusting for potential confounding factors such as age, sex, smoking, body mass index, hypertension, and lipoprotein subclasses (odds ratio = 3.389, 95% confidence interval 1.069–14.756). Marked difference between controls and T2DM subjects emerged from the analyses of the associations of the three enzyme activities and lipoprotein subclasses. Arylesterase was independently related with large HDL-C and small intermediate-density lipoprotein cholesterol (IDL-C) in controls while, along with lactonase, it was related with small low-density lipoprotein cholesterol LDL-C, all IDL-C subspecies, and very low-density lipoprotein cholesterol (VLDL-C) in T2DM (p<0.05for all). Concerning Lp-PLA2, there were significant relationships with small LDL-C, large IDL-C, and VLDL-C only among T2DM subjects. Our study showed that T2DM subjects have lower levels of PON1-arylesterase compared to controls and that T2DM occurrence may coincide with a shift of PON1 and Lp-PLA2 towards the more proatherogenic lipoprotein subclasses. The possibility of a link between the two observed phenomena requires further investigations.

Association of Dyslipidemia, Oxidative Stress, and Inflammation With Redox Status in VLDL, LDL, and HDL Lipoproteins in Patients With Renal Disease

Angiology ◽  
2018 ◽  
Vol 69 (10) ◽  
pp. 861-870 ◽  
Author(s):  
Milica Miljkovic ◽  
Aleksandra Stefanovic ◽  
Sanja Simic-Ogrizovic ◽  
Jelena Vekic ◽  
Natasa Bogavac-Stanojevic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Redox Status ◽  
Cardiovascular Complications ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Density

Some cardiovascular complications in patients with chronic kidney disease and end-stage renal disease may be caused by structurally and functionally modified lipoproteins. Redox status (advanced oxidation protein products [AOPPs]), prooxidant–antioxidant balance, total protein sulfhydryl (SH-groups), and paraoxonase 1 (PON1) activity were assessed in 77 renal patients and 20 controls. Lipoproteins were isolated using ultracentrifugation. PON1, PON3, and pentraxin-3 concentration were determined by enzyme-linked immunosorbent assay (ELISA). Dyslipidemia-Oxy-Inflammation (DOI) score was calculated as a sum of dyslipidemia, oxidative stress, and inflammation scores. The dyslipidemia score ( P < .001), oxy score ( P < .01), inflammation score (P < .001), and the DOI score ( P < .001) were higher in patient groups compared with controls. The very-low-density lipoprotein (VLDL) fraction contained the highest amount of AOPP ( P < .001) compared with other lipoprotein fractions in all groups. The low-density lipoprotein (LDL) fraction contained elevated AOPP in all groups compared with the high-density lipoprotein (HDL) fraction ( P < .001). Significant positive correlation was observed between AOPP in LDL fraction and DOI score (ρ = 0.510, P < .01). Dyslipidemia, oxidative stress, and inflammation play an interactive role in renal disease and are mutually associated with redox status in VLDL, LDL, and HDL lipoproteins in plasma of renal patients.

scholarly journals Lack of Association between Serum Paraoxonase 1 Activities and Increased Oxidized Low-Density Lipoprotein Levels in Impaired Glucose Tolerance and Newly Diagnosed Diabetes Mellitus

2003 ◽  
Vol 88 (4) ◽  
pp. 1711-1716 ◽  
Author(s):  
Steffi Kopprasch ◽  
Jens Pietzsch ◽  
Eberhard Kuhlisch ◽  
Juergen Graessler
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Newly Diagnosed ◽  
Diagnosed Diabetes ◽  
Serum Paraoxonase ◽  
Newly Diagnosed Diabetes

Several in vitro investigations showed that serum paraoxonase 1 (PON1) that is located on high-density lipoprotein reduces or prevents low-density lipoprotein (LDL) oxidation and therefore retards atherosclerosis. Accordingly, the well documented loss of PON1 activity in patients with overt diabetes mellitus was causally related to the development of micro- and macroangiopathy in the disease course. Because vascular complications start already in prediabetic states, e.g. impaired glucose tolerance (IGT), we investigated serum PON1 activities and circulating levels of oxidized LDL (oxLDL) in 125 IGT subjects, 75 patients with newly diagnosed diabetes mellitus type 2, and 403 individuals with normal glucose tolerance. Using three different substrates (paraoxon, phenylacetate, p-nitrophenylacetate) we found that PON1 activity is not significantly altered in IGT and diabetes mellitus subjects, respectively, when compared with normoglycemic controls. Both IGT subjects and diabetes mellitus patients had significantly increased levels of oxLDL in the circulation. However, serum PON1 activity variations and glutamine/arginine phenotype were not related to the levels of oxLDL. The data suggest that 1) PON1 activity loss is an event occurring later in the course of diabetes mellitus; and 2) PON1 does not affect oxidation of circulating LDL, at least in early diabetes mellitus.

Risk factors for cardiovascular diseases and development of prehypertension

2018 ◽  
pp. 37-43
Author(s):  
В.В. Шерстнев ◽  
М.А. Грудень ◽  
В.П. Карлина ◽  
В.М. Рыжов ◽  
А.В. Кузнецова ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
Left Ventricular ◽  
Optimal Blood Pressure

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

Antidyslipidemic and Antioxidant Activities of Matricaria pubescens (Desf.) Shultz.in Streptozotocin-Induced Diabetic Rats

2020 ◽  
Vol 18 ◽  
Author(s):  
Ayoub Amssayef ◽  
Bouchra Azzaou ◽  
Mohammed Ajebli ◽  
Mohamed Eddouks
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Activities ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Favorable Effect ◽  
Lipoprotein Profile ◽  
Phytochemical Compounds ◽  
Asteraceae Family

Aims: The study aimed to evaluate the antihyperlipidemic and antioxidant activities of Matricaria pubescens. Background: Matricaria pubescens (Desf.) Shultz belongs to Asteraceae family and it is commonly used traditionally for handling diabetes mellitus. Objective: The objective of this study was to assess the antioxidant activity of Matricaria pubescens (Desf.) Shultz and its effect on lipid and lipoprotein profile in normal and streptozotocin-induced diabetic rats. Methods: The effect of repeated (7 days of treatment) oral administration of the aqueous extract of aerial part of Matricaria pubescens (MPAE) at a dose of 40 mg/kg on lipid and lipoprotein profile was examined in normal and streptozotocin-induced diabetic rats. Furthermore, a preliminary phytochemical screening and the quantification of phenolic, flavonoid and tannin contents as well as the antioxidant activity using two methods (FRAP and ABTS) were carried out. Results: MPAE demonstrated a potent antidyslipidemic effect in diabetic rats by reducing serum levels of triglycerides, total cholesterol and low-density lipoprotein (LDL). In addition, the results showed that the extract is rich in several phytochemical compounds and revealed an important antioxidant activity. Conclusion: In summary, this study proved that Matricaria pubescens (Desf.) Shultz. has a favorable effect on diabetic dyslipidemia.

scholarly journals Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Giuseppina Russo ◽  
Basilio Pintaudi ◽  
Carlo Giorda ◽  
Giuseppe Lucisano ◽  
Antonio Nicolucci ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Diabetes Duration ◽  
Lipid Lowering ◽  
Age And Gender ◽  
Chd Risk ◽  
And Gender

Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men.Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM.Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P<0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups.Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk.

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