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High-density lipoprotein (HDL)-mediated inactivation of oxidized lipids in low-density lipoprotein (LDL). apoA-I-apolipoprotein A-I; GPx-gluthathione peroxidase; LCAT-lecithin:cholesterol acyltransferase; LOOH-lipid hydroperoxide; PAF-AH-platelet activating factor-acetylhydrolase; PON1-paraoxonase 1.
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Metabolic syndrome (MetS) is a high-risk condition for premature atherosclerotic vascular disease. Patients with MetS display a lipoprotein profile in which dense low-density lipoproteins (LDL), which are more susceptible to oxidation, predominate. Oxidation of lipoproteins can be attenuated in vivo by enzymatic and nonenzymatic antioxidant defense...
Context in source publication
Context 1
... states [6••,42,48] involving low HDL cholesterol phenotypes was selectively observed at late stages of LDL oxidation. Hence, it was most probably related to dysfunction involving mechanisms responsible for the inactivation of oxidized lipids (ie, removal and/or inactivation of lipid hydroperoxides) rather than of those preventing oxidation (Fig. 2). Abnormalities in the physi- cochemical properties of HDL may account for this ex vivo observation. In each study population (MetS, type 2 diabetes, and normotriglyceridemic, normocholesterolemic low HDL cholesterol phenotype), HDL 3 was enriched in triglycerides and depleted of cholesteryl esters [6••,42,48]. Such abnormalities were ...
Citations
... LDL-associated Apos act as communicators on oxidative stress-related signaling pathways to instigate reactive oxygen species (ROS) production and lead to the generation of atherogenic ox-LDL that has been widely identified as a major determinant driving the pathogenesis of atherosclerosis. Indeed, ox-LDL and its bioactive oxidized byproducts, such as lipid peroxides, aldehydes, hydroxyl sterols, and lysophosphatidylcholine, exhibit pro-atherogenic properties and contribute to atherogenesis by affecting manifold biological processes, containing the induction of cholesterol accumulation in macrophages as well as potent proinflammatory, proapoptotic and cytotoxic activities 70,71 . Meanwhile, various Apos accumulate in early atherosclerotic lesions and are considered as a defense mechanism against oxidative stress, which exerts antioxidative effects directly and indirectly through two synergistic manners to restrain atherosclerotic development in vivo. ...
Atherosclerosis as the leading cause of the cardiovascular disease is closely related to cholesterol deposition within subendothelial areas of the arteries. Significantly, early atherosclerosis intervention is the critical phase for its reversal. As atherosclerosis progresses, early foam cells formation may evolve into fibrous plaques and atheromatous plaque, ulteriorly rupture of atheromatous plaque increases risks of myocardial infarction and ischemic stroke, resulting in high morbidity and mortality worldwide. Notably, amphiphilic apolipoproteins (Apos) can concomitantly combine with lipids to form soluble lipoproteins that have been demonstrated to associate with atherosclerosis. Apos act as crucial communicators of lipoproteins, which not only can mediate lipids metabolism, but also can involve in pro-atherogenic and anti-atherogenic processes of atherosclerosis via affecting subendothelial retention and aggregation of low-density lipoprotein (LDL), oxidative modification of LDL, foam cells formation and reverse cholesterol transport (RCT) in macrophage cells. Correspondingly, Apos can be used as endogenous and/or exogenous targeting agents to effectively attenuate the development of atherosclerosis. The article reviews the classification, structure, and relationship between Apos and lipids, how Apos serve as communicators of lipoproteins to participate in the pathogenesis progression of early atherosclerosis, as well as how Apos as the meaningful targeting mass is used in early atherosclerosis treatment.
... Shakoei et al., in 2022, evaluated the levels of AGEs in 40 patients with AA and 40 controls, they found that AGEs serum levels in AA patients were higher than in healthy controls. The role of AGEs in inflammatory diseases is also well studied in skin diseases [78,79]. In PS, an increase in AGEs and advanced oxidation protein-products (AOPPs) and a reduction in PON have been observed. ...
Alopecia areata (AA) is a dermatological condition characterized by non-scarring hair loss. Exact etiopathogenesis of AA is still unknown although it is known that several factors contribute to the collapse of the hair-follicle (HF)-immune-privileged (IP) site. Oxidative stress (OS) plays an important role in skin diseases. The aim of this review was to clarify the role of OS in AA pathogenesis and diagnosis, and to discuss potential treatment options. Oxidative-stress markers are altered in serum and skin samples of patients with AA, confirming a general pro-oxidative status in patients with AA. OS induces MHC class I chain-related A (MICA) expression in HF keratinocytes that activates the receptor NKG2D, expressed in NK cells and CD8+ T cytotoxic cells leading to destabilization of the HF immune-privileged site through the production of IFN-γ that stimulates JAK1 and JAK2 pathways. OS also activates the KEAP1-NRF2 pathway, an antioxidant system that contributes to skin homeostasis. In addition, a decrease of ATG5 and LC3B in the hair matrix and an increase in p62 levels indicates a reduction of intrafollicular autophagy during the evolution of AA. Potential biomarkers of OS in AA could be: malondialdehyde (MDA), advanced glycation end-products (AGEs), and ischemic-modified albumin (IMA). JAK inhibitors are the new frontier in treatment of AA and the use of nutraceuticals that modulate the OS balance, in combination with standard treatments, represent promising therapeutic tools.
... The composition and biological functions of HDL are under a tight genetic control [100][101][102][103][104]. The biological effects of small, dense HDL are changed markedly in the individuals with insulin resistance and chronic inflammation [105][106][107]. Patients with type II diabetes typically have dyslipidemia characterized by high triglycerols and low HDLC Biomedicines 2021, 9, 600 8 of 17 levels [106]. ...
This review summarizes the main achievements in basic and clinical research of atherosclerosis. Focusing on desialylation as the first and the most important reaction of proatherogenic pathological cascade, we speak of how desialylation increases the atherogenic properties of low density lipoproteins and decreases the anti-atherogenic properties of high density lipoproteins. The separate sections of this paper are devoted to immunogenicity of lipoproteins, the enzymes contributing to their desialylation and animal models of atherosclerosis. In addition, we evaluate the available experimental and diagnostic protocols that can be used to develop new therapeutic approaches for atherosclerosis.
... Moreover, exposure to high altitude has been associated with increased oxidative stress and lipid peroxidation (10). Oxidative stress can lead to both quantitative and qualitative alterations in lipoproteins, such as HDL particles (11). In this regard, paraoxonase 1 (PON1), which is a main contributor to HDL antioxidant activity (12), has been shown to be altered under oxidant conditions (13). ...
Background:
High altitude is associated with hypobaric hypoxia, and metabolic modifications. In particular, alterations to lipoprotein-associated enzymes have been reported under hypoxia.
Objective:
To determine the association between paraoxonase 1 (PON-1) and Cholesteryl-ester transfer protein (CETP) activities and altitude in two groups of Argentinean Indigenous schoolchildren living at different altitudes.
Methods:
A cross-sectional study compared 151 schoolchildren from San Antonio de los Cobres (SAC), 3,750 m, with 175 schoolchildren from Chicoana (CH), 1,400 m. Anthropometric data, lipids, apolipoprotein (apo) A-I, apo B, plus PON-1 and CETP activities were determined.
Results:
The prevalence of overweight/obesity was significantly lower in SAC than in CH. Z- BMI (0.3 vs 0.7), Apo A-I/Apo B (1.67 vs. 1.85) and PON-1 (170 vs. 243 nmol/mL.min) were significantly lower in SAC than in CH, respectively. Total cholesterol (156 vs 144 mg/dL), triglycerides (TG) (119 vs. 94 mg/dL), apo A-I (133 vs. 128 mg/dL), apo B (84 vs. 73 mg/dL), hematocrit (48 vs. 41%), transferrin (295 vs. 260 mg/dL) and CETP (181 vs. 150%/mL.h) were significantly higher in SAC than in CH. There was a significant univariate association between altitude and transferrin (r0.38), hematocrit (r0.75), TG (r0.24), apo B (r0.29), PON-1 (r-0.40), and CETP (r0.37). Multiple linear regression analyses showed that altitude was significantly associated with children's TG (β = 0.28, R2 = 0.14), HDL-C (β = ‒0.27; R2 = 0.23), apo B (β = 0.32; R2 = 0.14), CETP (β = 0.38; R2 = 0.15) and PON-1 (β = ‒0.36; R2 = 0.16), adjusted for age, gender and BMI.
Conclusion:
SAC children presented a more atherogenic lipid profile, plus lower PON1 and higher CETP activities, than CH children.
... Indeed, cholesterol efflux capacity, antioxidative activity toward LDL oxidation, antithrombotic activity in human platelets, anti-inflammatory activity, and antiapoptotic activity in endothelial cells were all enriched in the small, dense, protein-rich HDL3c relative to other HDL subfractions (6,9). Importantly, biological activities of small, dense HDL have been reported to be markedly altered in patients with insulin resistance and inflammation (10)(11)(12). ...
High-density lipoprotein (HDL) possesses multiple biological activities; small, dense HDL3c particles displaying distinct lipidomic composition exert potent antiatherogenic activities which can be compromised in dyslipidemic, hyperglycemic insulin-resistant states. However, it remains indeterminate (i) whether such functional HDL deficiency is related to altered HDL composition, and (ii) whether it originates from atherogenic dyslipidemia, dysglycemia, or both. In the present work we analyzed compositional characteristics of HDL subpopulations and functional activity of small, dense HDL3c particles in treatment-naïve patients with well-controlled (n=10) and poorly-controlled (n=8) type 2 diabetes (T2D) and in normolipidemic age- and sex-matched controls (n=11). Our data reveal that patients with both well- and poorly-controlled T2D displayed dyslipidemia and low-grade inflammation associated with altered HDL composition. Such compositional alterations in small, dense HDL subfractions were specifically correlated with plasma HbA1c levels. Further analysis using a lipidomic approach revealed that small, dense HDL3c particles from T2D patients with poor glycemic control displayed additional modifications of their chemical composition. In parallel, antioxidative activity of HDL3c towards oxidation of low-density lipoprotein was diminished. These findings indicate that defective functionality of small, dense HDL particles in patients with T2D is not only affected by the presence of atherogenic dyslipidemia, but also by the level of glycemic control, reflecting compositional alterations of HDL.
... Such metabolic alterations are in large part due to elevated activity of cholesteryl ester transfer protein (CETP) in the presence of elevated levels of TG-rich lipoprotein acceptors 3 ; indeed, CETP mediates the transfer of cholesteryl esters (CEs) from HDL to proatherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein (VLDL) to HDL. 3 Such compositional modifications are accompanied by marked alterations in the biological function of the lipoproteins. 4 On the one hand, the preponderance of small, dense LDL particles, which are highly susceptible to oxidative modification, increases the overall oxidizability of the circulating LDL pool. On the other hand, the capacity of HDL, and primarily of potently antioxidative, small, dense HDL3c particles to protect LDL from oxidation, is deficient among patients with MetS 5 and equally among patients with type 2 diabetes 6 and in those with isolated low HDL-C levels. ...
Metabolic syndrome (MetS) is associated with altered lipoprotein metabolism and impairment in the functionality of small, dense HDL particles secondary to compositional alterations.Objective
To investigate the capacity of a lifestyle program to improve the composition and antioxidative function (AOX) of small dense HDL3c in MetS.Methods
Patients with MetS (n=33) not taking lipid-lowering drugs were recruited to follow a 12-week educational program to reduce caloric intake and to increase physical activity. HDL subfractions were preparatively isolated by isopycnic density gradient ultracentrifugation. AOX of HDL3c was assessed as its capacity to inhibit LDL oxidation induced by an azoinitiator.ResultsAOX of HDL3c was significantly improved (mean reduction in the propagation rate of LDL oxidation by HDL3c, -6.8%, p=0.03) and systemic oxidative stress, assessed as plasma levels of 8-isoprostanes, tended to decrease in normocholesterolemic MetS patients (LDL-cholesterol (LDL-C)
... Recently, it was hypothesized that the administration of appropriate antioxidants as adjuvant agents, in addition to the usual dietary treatment and supplementation, may prevent neurological damage in PKU patients (Ribas et al. 2011). Considering the interplay between oxidative stress and conditions like obesity and cardiovascular diseases (Ando and Fujita 2009;Farbstein et al. 2010;Furukawa et al. 2004;Hansel et al. 2006;Holvoet et al. 2008a, b), this review aims to establish a new perspective for oxidative stress surveillance in PKU patients translated into future directions for clinical follow-up and educational goals, in order to optimize health status during their life-span. ...
... LDL oxidation favours atherosclerosis and has been associated with abdominal obesity (Aviram et al. 2005;Efrat and Aviram 2010;Florentin et al. 2008;Garin et al. 2005;Holvoet et al. 2008a, b;Précourt et al. 2010;Rizzo et al. 2009;Witztum and Steinberg 2001). Consequently, the close link between cardiovascular diseases, obesity and oxidative stress (Ando and Fujita 2009;Farbstein et al. 2010;Furukawa et al. 2004;Hansel et al. 2006;Holvoet et al. 2008a, b;Hopps et al. 2010) increases the interest in the three known PONs, considering their importance on tissue and blood oxidative stress control (Aviram et al. 2005;Camps et al. 2009;Getz and Reardon 2004;Ng et al. 2001;Précourt et al. 2010). Just as for LDL oxidation (Sanayama et al. 2011), there is just one study evaluating PON1 activity in PKU: in the group of patients with higher Phe levels the total antioxidant capacity is lower combined with a decreased PON1 activity (Schulpis et al. 2007). ...
Phenylketonuria represents the most prevalent inborn error of amino acid metabolism. In early diagnosed patients adequate and continued dietary treatment results in a good neurologic outcome. Natural protein and phenylalanine-restricted diet, even if rich in fruits and vegetables, represents a serious risk for nutritional deficiencies, albeit universally accepted. In the last few years, a growing number of reports have been describing oxidative stress as a concern in phenylketonuric patients. The diet itself includes good sources of dietary antioxidants (phytochemicals, some vitamins and minerals) but also a risk factor for some deficiencies (selenium, zinc, ubiquinone-10 and L-carnitine). Additionally, the extreme stringency of the diet may impose a reduced synthesis of endogenous antioxidants (like ubiquinone-10 and glutathione). Furthermore, increased phenylalanine levels, and its metabolites, may enhance the endogenous synthesis of reactive species and free radicals and/or interfere with the endogenous synthesis of enzymatic antioxidants (like glutathione peroxidase). Therefore, oxidative stress will probably increase, mainly in late diagnosed patients or in those with bad metabolic control. Considering the known association between oxidative stress, obesity and cardiovascular disease, it seems advisable to look further to the impact of oxidative stress on body macromolecules and structures (like lipoprotein oxidation), especially in phenylketonuric patients with late diagnosis or bad metabolic control, in order to prevent future increased risks. Recommendations for PKU patient's clinical follow-up improvement and educational goals are included.
... The deregulation of peroxiredoxin-2 has been shown previously in murine bone marrow [27] and murine serum proteome following exposure of the mouse skin [37]. Other proteins important in the protection against oxidative damage383940 such as glutathione transferase, complement C3, apolipoprotein E, and a-crystallin B were also found to be upregulated in this study. ROS is known to cause a number of post-translational modifications of proteins, including carbonylation. ...
Accidental nuclear scenarios lead to environmental contamination of unknown level. Immediate radiation-induced biological responses that trigger processes leading to adverse health effects decades later are not well understood. A comprehensive proteomic analysis provides a promising means to identify and quantify the initial damage after radiation exposure. Early changes in the cardiac tissue of C57BL/6 mice exposed to total body irradiation were studied, using a dose relevant to both intentional and accidental exposure (3 Gy gamma ray). Heart tissue protein lysates were analyzed 5 and 24 h after the exposure using isotope-coded protein labeling (ICPL) and 2-dimensional difference-in-gel-electrophoresis (2-D DIGE) proteomics approaches. The differentially expressed proteins were identified by LC-ESI-MS-MS. Both techniques showed similar functional groups of proteins to be involved in the initial injury. Pathway analyses indicated that total body irradiation immediately induced biological responses such as inflammation, antioxidative defense, and reorganization of structural proteins. Mitochondrial proteins represented the protein class most sensitive to ionizing radiation. The proteins involved in the initial damage processes map to several functional categories involving cardiotoxicity. This prompts us to propose that these early changes are indicative of the processes that lead to an increased risk of cardiovascular disease after radiation exposure.
... En estas condiciones se produce un desequilibrio en la relación entre factores prooxidantes y protectores de oxidación observable en el envejecimiento normal. Podría decirse que el síndrome metabólico y el estrés oxidativo asociado serían propios de un proceso de envejecimiento acelerado 21 . ...
Rev Fed Arg Cardiol 2011; 40 (2): 143-151 143 E l consumo de bebidas cola carbonatadas se ha aso-ciado con aumento de peso y obesidad 1 , y se ha triplicado, en niños y adolescentes, en los últimos 30 años, reflejando un notable incremento respecto de re-gistros anteriores 2 . Un relevamiento de datos poblacio-nales (National Diet and Nutrition Survey 3) reveló que las gaseosas representan el 56% de la ingesta líquida de niños y adolescentes entre 4 y 18 años, seguida por la leche (18%) y el agua (9%). La relación entre el consumo de bebidas gaseosas azucaradas y la aparición de obesidad ha sido docu-mentada tanto en niños y adolescentes 4 como en adul-tos 5 . Por consiguiente, es de vital importancia ahondar en el conocimiento de los efectos que el consumo exage-rado de estas bebidas produce a nivel metabólico y car-diovascular 3,6 . Existe acuerdo en que la ingesta de la fructosa presente en estas bebidas, a diferencia de la glucosa, no estimularía la liberación de insulina y leptina, no produciendo saciedad e incrementando in-directamente el consumo calórico 6 . En los últimos años se ha enfatizado la importancia del síndrome metabólico (SM) en relación con un ma-yor riesgo de desarrollo de diabetes mellitus tipo 2 y enfermedad cardiovascular asociada 7 , siendo esta la ARTICULOS ORIGINALES Manifestaciones bioquímicas, ecocardiográficas y anatomopatológicas asociadas con el síndrome metabólico inducido por Coca-Cola ® en la rata El consumo de bebidas gaseosas se ha triplicado en los últimos veinte años. Objetivo: investigar los efectos metabólicos y cardiovasculares de la ingesta de Coca-Cola ® y Coca-Cola ® light en ratas. Material y método: durante 6 meses de tratamiento, se estudiaron 48 ratas Wistar macho que fueron divididas en tres grupos, según la bebida utilizada: Coca-Cola ® (C), Coca-Cola ® light (L) o agua (A). A su término todos los animales bebieron agua durante otros 6 meses (lavado). Se obtuvieron ecocardiografía y registro de presión sistólica en animales despiertos a los tiempos indicados. Se midieron los niveles plasmáticos de ␣ ␣ ␣ ␣ ␣-tocoferol, ubiquinona-10, glucosa, triglicéridos, colesterol total y de alta densidad plasmáticos a los 6 meses (tratamiento) y a los 12 meses (lavado) desde el inicio del estudio. Resultados: a los 6 meses los animales del grupo C mostraron (vs grupo A): aumento de peso (+7 ± 1%; p < 0,01), mayor consumo líquido (× 1,7 veces; p < 0,001), hipertensión sistólica (+7,5 ± 0,5%; p < 0,01), ingesta sólida disminuida (-31%; p < 0,001), hipertrigliceridemia (× 3 veces; p < 0,01), hiperglucemia (+15 ± 1%; p < 0,05) y menores niveles de ubiquinona-10 (-52 ± 2%; p < 0,05). Estos cambios revirtieron a los 12 meses, excepto la hipertrigliceridemia y los niveles bajos de ubiquinona-10. Se observó dilatación ventricular y aumento del volumen minuto sin cambios en la frecuencia cardíaca en los grupos C y L, que revirtieron luego del lavado. Las autopsias revelaron casos aislados de esteatosis hepática no relacionados con el tratamiento, un caso de nefropatía crónica progresiva en C, cambios en el calibre vascular retiniano (relacion arteriola: vénula) y angiogénesis extrarretiniana. Conclusión: el consumo prolongado de Coca-Cola ® derivó en: estrés oxidativo y perfil bioquímico característico compatible con síndrome metabólico, remodelación del ventrículo izquierdo y alteraciones arteriales retinianas. Los hallazgos avalan la confiabilidad de este modelo para su uso en futuros estudios que arrojen informa-ción con potencial transferencia al ámbito clínico. Palabras clave: Síndrome metabólico. Bebidas cola. Estrés oxidativo. Coenzima Q 10 .
... Experimentally-induced metabolic syndrome induces oxidative stress-related biochemical changes resembling those appearing along life-span. Present findings are consistent with and add further support to the idea that metabolic syndrome is a high-risk condition for premature aging-related changes [12]. The authors would like to thank Biochem. ...
