scholarly journals Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression

Stroke ◽  
2021 ◽  
Author(s):  
Morsaleh Ganji ◽  
Valentina Nardi ◽  
Megha Prasad ◽  
Kyra L. Jordan ◽  
Melanie C. Bois ◽  
...  
Keyword(s):  
Risk Factors ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Carotid Plaque ◽  
High Density ◽  
Interquartile Range ◽  
High Density Lipoproteins ◽  
Atherosclerotic Plaques ◽  
Cholesterol Levels ◽  
Plaque Destabilization

Background and Purpose: XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors. Methods: Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured. Results: Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P <0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P <0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels ( P =0.010, r =−0.30) and directly with circulating uric acid levels ( P <0.001, r =0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P <0.001). Conclusions: XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.

scholarly journals High-density lipoprotein remodelled in hypercholesterolaemic blood induce epigenetically driven down-regulation of endothelial HIF-1α expression in a preclinical animal model

2019 ◽  
Vol 116 (7) ◽  
pp. 1288-1299 ◽  
Author(s):  
Soumaya Ben-Aicha ◽  
Rafael Escate ◽  
Laura Casaní ◽  
Teresa Padró ◽  
Esther Peña ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Down Regulation ◽  
Cholesterol Levels ◽  
In Vivo Effects ◽  
Mirna Content

Abstract Aims High-density lipoproteins (HDLs) are circulating micelles that transport proteins, lipids, and miRNAs. HDL-transported miRNAs (HDL-miRNAs) have lately received attention but their effects on vascular cells are not fully understood. Additionally, whether cardiovascular risk factors affect HDL-miRNAs levels and miRNA transfer to recipient cells remains equally poorly known. Here, we have investigated the changes induced by hypercholesterolaemia on HDL-miRNA levels and its effect on recipient endothelial cells (ECs). Methods and results Pigs were kept on a high-fat diet (HC; n = 10) or a normocholesterolaemic chow (NC; n = 10) for 10 days reaching cholesterol levels of 321.0 (229.7–378.5) mg/dL and 74.0 (62.5–80.2) mg/dL, respectively. HDL particles were isolated, purified, and quantified. HDL-miRNA profiling (n = 149 miRNAs) of HC- and NC-HDLs was performed by multipanel qPCR. Cell cultures of porcine aortic ECs were used to determine whether HDL-miRNAs were delivered to ECs. Potential target genes modulated by miRNAs were identified by bioinformatics and candidate miRNAs were validated by molecular analysis. In vivo effects in the coronary arteries of normocholesterolaemic swine administered HC- or NC-HDLs were analysed. Among the HDL-miRNAs, four were found in different amounts in HC- and NC-HDL (P &lt; 0.05). miR-126-5p and -3p and miR-30b-5p (2.7×, 1.7×, and 1.3×, respectively) were found in higher levels and miR-103a-3p and miR-let-7g-5p (−1.6×, −1.4×, respectively) in lower levels in HC-HDL. miR-126-5p and -3p were transferred from HC-HDL to EC (2.5×; P &lt; 0.05), but not from NC-HDL, by a SRB1-mediated mechanism. Bioinformatics revealed that HIF1α was the miR-126 target gene with the highest predictive value, which was accordingly found to be markedly reduced in HC-HDL-treated ECs and in miR126 mimic transfected ECs. In vivo validation confirmed that HIF1α was diminished in the coronary endothelial layer of NC pigs administered HC-HDL vs. those administered NC-HDL (P &lt; 0.05). Conclusion Hypercholesterolaemia induces changes in the miRNA content of HDL enhancing miR126 and its delivery to ECs with the consequent down-regulation of its target gene HIF1α.

Statin treatment is associated with reduced toll-like receptor 4 immunohistochemical expression on carotid atherosclerotic plaques: a novel effect of statins

Vascular ◽  
2011 ◽  
Vol 19 (6) ◽  
pp. 320-326 ◽  
Author(s):  
Athanasios Katsargyris ◽  
Chris Klonaris ◽  
Sotirios Tsiodras ◽  
Elias Bastounis ◽  
Athanasios Giannopoulos ◽  
...  
Keyword(s):  
Carotid Plaque ◽  
Statin Treatment ◽  
Atherosclerotic Plaques ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Immunohistochemical Expression ◽  
Toll Like Receptor 4 ◽  
Over Expression ◽  
Plaque Stabilization ◽  
Plaque Destabilization

Toll-like receptor 4 (TLR4) has been recently implicated in inflammatory pathways involved in carotid plaque destabilization. Given that statins have plaque stabilization and inflammation reduction effects, we investigated whether TLR4 expression on carotid atherosclerotic plaques correlates with statin intake. Carotid atherosclerotic plaques were obtained on 140 patients (preoperative statin intake, n = 70). TLR4 immunohistochemical expression was investigated in endothelial cells (ECs), macrophages (MACs) and smooth muscle cells (SMCs) of carotid atheroma. TLR4 positivity, over-expression and intensity of immunostaining were compared in statin versus no-statin users. The results of this study showed that statin users had a significantly lower expression of TLR4 in ECs ( P = 0.02, 0.001, 0.006 for TLR4 positivity, increased intensity and over-expression, respectively). Similarly, TLR4 positivity was less pronounced in carotid plaque MACs of statin users ( P = 0.03). No carotid specimen with increased EC TLR4 intensity or over-expression was observed among statin users. The prevalence of any cerebrovascular accident was 61.4% in the ‘no statin’ versus 18.6% in the ‘statin’ group (odds ratio for statin use: 0.14, 95% CI: 0.07–0.31, P < 0.001). In conclusion, statin treatment is associated with attenuated TLR4 expression on human carotid atherosclerotic plaques and a reduced risk of carotid-related cerebrovascular events. TLR4 may potentially mediate statins' plaque stabilization effects. Further investigation is necessary.

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients

2015 ◽  
Vol 26 (5) ◽  
pp. 901-908 ◽  
Author(s):  
Mehmet Gündüz ◽  
Sevim Çakar ◽  
Pınar Kuyum ◽  
Balahan Makay ◽  
Nur Arslan
Keyword(s):  
Risk Factors ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Platelet Volume ◽  
Cholesterol Levels ◽  
The Mean ◽  
Serum Phenylalanine

AbstractBackgroundPrevious studies investigating the known risk factors of atherosclerosis in phenylketonuria patients have shown conflicting results. The primary aim of our study was to investigate the serum atherogenic markers in adolescent classical phenylketonuria patients and compare these parameters with healthy peers. The secondary aim was to compare these atherogenic markers in well-controlled and poorly controlled patients.MethodsA total of 59 patients (median age: 12.6 years, range: 11–17 years) and 44 healthy controls (median age: 12.0 years, range: 11–15 years) were enrolled in our study. Phenylketonuria patients were divided into two groups: well-controlled (serum phenylalanine levels below 360 µmol/L; 24 patients) and poorly controlled patients (serum phenylalanine levels higher than 360 µmol/L).ResultsThe mean high-density lipoprotein cholesterol levels of well-controlled patients (1.0±0.2 mmol/L) were significantly lower compared with poorly controlled patients and controls (1.1±0.2 mmol/L, p=0.011 and 1.4±0.2 mmol/L, p<0.001, respectively). Poorly controlled patients had lower high-density lipoprotein cholesterol levels than healthy controls (p=0.003). Homocysteine levels of both well-controlled (9.8±6.4 µmol/L) and poorly controlled (9.2±5.6 µmol/L) patients were higher compared with controls (5.8±1.8 µmol/L, p<0.01). The mean platelet volume of well-controlled patients (9.5±1.1 fL) was higher than that of poorly controlled patients and controls (8.9±0.8 fL, p=0.024 and 7.7±0.6 fL, p<0.001, respectively).ConclusionLower high-density lipoprotein cholesterol and higher homocysteine and mean platelet volume levels were detected in phenylketonuria patients. In particular, these changes were more prominent in well-controlled patients. We conclude that phenylketonuria patients might be at risk for atherosclerosis, and therefore screening for atherosclerotic risk factors should be included in the phenylketonuria therapy and follow-up in addition to other parameters.

scholarly journals The Complex Fate in Plasma of Gadolinium Incorporated into High-Density Lipoproteins Used for Magnetic Imaging of Atherosclerotic Plaques

2013 ◽  
Vol 24 (6) ◽  
pp. 1039-1048 ◽  
Author(s):  
Alessandra Barazza ◽  
Courtney Blachford ◽  
Orli Even-Or ◽  
Victor A. Joaquin ◽  
Karen C. Briley-Saebo ◽  
...  
Keyword(s):  
High Density ◽  
High Density Lipoproteins ◽  
Atherosclerotic Plaques ◽  
Magnetic Imaging

scholarly journals The Content of Low Density Lipoprotein, High Density Lipoproteins, Cholesterol on Pen Shells (Atrina Pectinata) Fish Catch in Kenjeran Surabaya

2020 ◽  
Vol 7 (2) ◽  
pp. 51
Author(s):  
Rio Khalif Eldiaz ◽  
Agustono Agustono ◽  
Kustiawan Tri Pursetyo
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Digestive Organs ◽  
Cholesterol Levels ◽  
Fish Catch ◽  
Atrina Pectinata

Pen Shells (A. pectinata) Is one type of a clam that is mostly consumed, Cholesterol levels included in a category high. Although the high cholesterol levels. Shells also contain levels commonly called ldl cholesterol evil . Having shells also levels of hdl, Cholesterol levels total normal in plasma adults is of 120 until 200 mg/dl. Different from its function at the time of cholesterol levels normal, the higher cholesterol levels in the blood, the greater the risk of atherosclerosis also. The purpose of this research is to get information about ldl levels , hdl and cholesterol contained in shells kampak , as well as to determine the shells kampak who most worthy for consumption. Parameter that observed in this research was ldl , hdl , cholesterol .This study using methods descriptive against the difference levels of low density lipopprotein ( ldl ) and high-density lipoproteins ( hdl ) and cholesterol in any bivalve hatchets the results of catch fishermen in kenjeran surabaya. Average levels of ldl on pen shells (A. pictinata) In the meat is 30,990 mg/100g, in the muscle is 28,329 mg/100g and in the Digestive organs is 25,225 mg/100g ; The average levels of hdl on pen shells (A. pictinata) in the meat is 96,772 mg/100g, in the muscle is 87,139 mg/100g and in the Digestive organs is 67,516 mg/100g ; average levels of cholesterol on pen shells (A. pictinata) in the meat is 165,609 mg/100g, in the muscle is 147,382 mg/100g and in the Digestive organs is 114,551 mg/100g. Levels of LDL, HDL and cholesterol Lead to results same that is the most number are located on the meat, then muscle and at least there are on an disgestive organ.

scholarly journals Fatores de Risco Cardiovascular e Medidas Antropométricas em Crianças e Adolescentes / Cardiovascular Risk Factors and Anthropometric Measures in Children and Adolescents

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Jayne Ramos Araujo Moura ◽  
Eugênio Barbosa de Melo Júnior ◽  
Mayara Vidal Torres Pimenta ◽  
Cyléa Abdalla de Miranda Silva ◽  
Ana Míria De Oliveira Batista ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Children And Adolescents ◽  
Cardiovascular Risk Factors ◽  
High Density ◽  
High Density Lipoproteins ◽  
Anthropometric Measures

O objetivo do estudo foi analisar a associação entre alterações nas medidas antropométricas e a frequência de fatores de risco cardiovascular em crianças e adolescentes. Estudo transversal, com amostra de 421 crianças e adolescentes. A coleta de dados foi realizada no período de agosto a novembro de 2014, por meio do preenchimento do formulário com informações referentes a identificação, aos aspectos socioeconômicos, às medidas antropométricas, à aferição da pressão arterial e de prática de atividades físicas, além de exames bioquímicos.Os principais resultados encontrados foram: 59,6% eram do sexo feminino, com idade média de 11,4 anos. Aqueles que apresentaram maiores índices de massa corporal e/ou circunferência da cintura alterada tinham mais chances de apresentar pressão arterial sistólica elevada, triglicerídeo elevado e high density lipoproteins – colesterol baixo.Conclui-se que aqueles que estavam acima do peso e/ou com excesso de adiposidade central apresentaram expressivas frequências de fatores de risco, como hipertensão arterial e desordens no perfil lipídico, para o desenvolvimento de doenças cardiovasculares.

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