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1.
PLoS One ; 16(4): e0250328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33905435

RESUMO

BACKGROUND: Data on the burden of dyslipidaemia among people with HIV undergoing antiretroviral therapy (ART) in sub-Saharan Africa are limited and little is known about the factors contributing for poor lipid profiles. The aim of this study was to determine the prevalence of dyslipidaemia and factors associated with lipid levels among HIV-infected patients receiving first-line combination ART in North Shewa, Ethiopia. METHODS: A cross-sectional study was conducted between April and December 2018 among 392 HIV-infected adults receiving first-line ART for at least six months at the ART clinic of Mehal Meda Hospital in North Shewa, Ethiopia. Blood samples were collected for determination of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and CD4 counts. Logistic regression analysis was used to determine factors associated with lipid abnormalities. RESULTS: The prevalence of dyslipidaemia was 59.9% (95% CI 55.0-64.7%). High TC, high TG, low HDL-c, and high LDL-c were obtained in 47.3%, 30.9%, 19.4% and 29.6%, respectively. Fifty-four participants (13.8%) had high ratio of TC/HDL-c (TC/HDL-c ratio ≥ 5). Older age was independently associated with high TC (AOR = 2.51, 95% CI 1.64-3.84), high TG (AOR = 2.95, 95% CI 1.85-4.71), low HDL-c (AOR = 2.02, 95% CI 1.17-3.50), and high LDL-c (AOR = 3.37, 95% CI 2.08-5.47). Living in an urban area (AOR = 2.61, 95% CI 1.16-6.14) and smoking (AOR = 3.61, 95% CI 1.06-12.34) were associated with low HDL-c. Participants with longer duration of ART use were more likely to have high TG (AOR = 1.86, 95% CI: 1.13-3.07), low HDL-c (AOR = 3.47, 95% CI: 1.75-6.80), and high LDL-c (AOR = 2.20, 95% CI 1.30-3.71). High BMI was independently associated with higher TC (AOR = 2.43, 95% CI 1.19-4.97), high TG (AOR = 4.17, 95% CI 2.01-8.67) and high LDL-c (AOR = 6.53, 95% CI 3.05-13.98). CONCLUSIONS: We found a high prevalence of dyslipidaemia among HIV-infected patients receiving first-line ART in North Shewa, Ethiopia. There is a need for monitoring of blood lipid levels in patients with HIV on long term first-line ART with a special attention to be focused on older age, urban residents, longer duration of ART use, high BMI and smokers.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Dislipidemias/epidemiologia , Infecções por HIV/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , HDL-Colesterol/sangue , HDL-Colesterol/imunologia , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Estudos Transversais , Dislipidemias/tratamento farmacológico , Dislipidemias/imunologia , Dislipidemias/virologia , Etiópia/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Triglicerídeos/sangue , Triglicerídeos/imunologia , População Urbana
2.
J Cosmet Dermatol ; 19(5): 1219-1223, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31490625

RESUMO

BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disorder that may be associated with metabolic disorders. The relation between lipid profile in acne is not widely investigated. Chitinase-3-like protein 1 (YKL-40) has been found to be implicated in different inflammatory conditions. AIMS: We aimed at investigating the role YKL-40 in acne pathogenesis and associated dyslipidemia in acne patients. PATIENTS/METHODS: This study included 50 acne vulgaris patients and 30 matched control subjects. Serum YKL-40 in addition to lipid profile were assessed in all studied subjects. RESULTS: Serum YKL-40 level was significantly elevated in acne patients than healthy controls (P < .001). We also found a significant positive correlations between serum YKL-40, serum TGs, TC, and LDL-C (P value: .022, .001, .017 respectively) while, a significant negative correlation between serum YKL-40 and HDL-c (P value: .036) was detected. CONCLUSION: Our study results suggest that YKL-40 might have a role in AV pathogenesis. In addition, it could provide a new potential link between inflammation and dyslipidemia observed in acne patients.


Assuntos
Acne Vulgar/etiologia , Proteína 1 Semelhante à Quitinase-3/sangue , Dislipidemias/complicações , Inflamação/imunologia , Acne Vulgar/sangue , Acne Vulgar/metabolismo , Adolescente , Estudos de Casos e Controles , Proteína 1 Semelhante à Quitinase-3/imunologia , HDL-Colesterol/sangue , HDL-Colesterol/imunologia , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , LDL-Colesterol/metabolismo , Dislipidemias/sangue , Dislipidemias/imunologia , Feminino , Humanos , Inflamação/sangue , Lipidômica , Masculino , Triglicerídeos/sangue , Triglicerídeos/imunologia , Triglicerídeos/metabolismo , Adulto Jovem
3.
BMC Med ; 17(1): 197, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672136

RESUMO

BACKGROUND: Dyslipidemia and inflammation are closely interrelated contributors in the pathogenesis of atherosclerosis. Disorders of lipid metabolism initiate an inflammatory and immune-mediated response in atherosclerosis, while low-density lipoprotein cholesterol (LDL-C) lowering has possible pleiotropic anti-inflammatory effects that extend beyond lipid lowering. MAIN TEXT: Activation of the immune system/inflammasome destabilizes the plaque, which makes it vulnerable to rupture, resulting in major adverse cardiac events (MACE). The activated immune system potentially accelerates atherosclerosis, and atherosclerosis activates the immune system, creating a vicious circle. LDL-C enhances inflammation, which can be measured through multiple parameters like high-sensitivity C-reactive protein (hsCRP). However, multiple studies have shown that CRP is a marker of residual risk and not, itself, a causal factor. Recently, anti-inflammatory therapy has been shown to decelerate atherosclerosis, resulting in fewer MACE. Nevertheless, an important side effect of anti-inflammatory therapy is the potential for increased infection risk, stressing the importance of only targeting patients with high residual inflammatory risk. Multiple (auto-)inflammatory diseases are potentially related to/influenced by LDL-C through inflammasome activation. CONCLUSIONS: Research suggests that LDL-C induces inflammation; inflammation is of proven importance in atherosclerotic disease progression; anti-inflammatory therapies yield promise in lowering (cardiovascular) disease risk, especially in selected patients with high (remaining) inflammatory risk; and intriguing new anti-inflammatory developments, for example, in nucleotide-binding leucine-rich repeat-containing pyrine receptor inflammasome targeting, are currently underway, including novel pathway interventions such as immune cell targeting and epigenetic interference. Long-term safety should be carefully monitored for these new strategies and cost-effectiveness carefully evaluated.


Assuntos
Aterosclerose/imunologia , LDL-Colesterol/imunologia , Inflamação/imunologia , Anti-Inflamatórios/uso terapêutico , Aterosclerose/prevenção & controle , Biomarcadores , Proteína C-Reativa/imunologia , Humanos , Inflamação/prevenção & controle
4.
Mol Biol Rep ; 46(3): 3257-3264, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31073913

RESUMO

The aim of this work was to study the effect of the carbon source (glycerol, sucrose, glucose or a sucrose/glucose mixture) on the production of the anti LDL (-) single-chain variable fragment (scFv) by the recombinant Pichia pastoris SMD 1168 strain as well as on the cell size. The use of glucose as a carbon source in the growth phase led to a remarkable increase in cell size compared with glycerol, while the smallest cells were obtained with sucrose likely due to the occurrence of an energetic stress. The scFv concentration seemed to be related to cell number rather than to cell concentration, which in its turn showed no significant dependence on the carbon source. Yeast cells grown on sucrose had a mean diameter (0.736 ± 0.097 µm) about 35% shorter than those grown on glucose and allowed for the highest final concentration of the scFv antibody fragment (93.7 ± 0.2 mg/L). These results demonstrate that sucrose is the best carbon source for the expression of such an antibody fragment by the recombinant P. pastoris strain, which may be very useful for the diagnostic analysis of the so-called "bad cholesterol".


Assuntos
Carbono/metabolismo , LDL-Colesterol/imunologia , Pichia/metabolismo , Tamanho Celular , Fermentação , Expressão Gênica , Glicerol , Pichia/genética , Proteínas Recombinantes/genética , Anticorpos de Cadeia Única/metabolismo
5.
Ann Med ; 50(6): 461-484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29976096

RESUMO

Inflammatory changes are responsible for maintenance of the atherosclerotic process and may underlie some of the most feared vascular complications. Among the multiple mechanisms of inflammation, the arterial deposition of lipids and particularly of cholesterol crystals is the one responsible for the activation of inflammasome NLRP3, followed by the rise of circulating markers, mainly C-reactive protein (CRP). Elevation of lipoproteins, LDL but also VLDL and remnants, associates with increased inflammatory changes and coronary risk. Lipid lowering medications can reduce cholesterolemia and CRP: patients with elevations of both are at greatest cardiovascular (CV) risk and receive maximum benefit from therapy. Evaluation of the major drug series indicates that statins exert the largest LDL and CRP reduction, accompanied by reduced CV events. Other drugs, mainly active on the triglyceride/HDL axis, for example, PPAR agonists, may improve CRP and the lipid pattern, especially in patients with metabolic syndrome. PCSK9 antagonists, the newest most potent medications, do not induce significant changes in inflammatory markers, but patients with the highest baseline CRP levels show the best CV risk reduction. Parallel evaluation of lipids and inflammatory changes clearly indicates a significant link, both guiding to patients at highest risk, and to the best pharmacological approach. Key messages Lipid lowering agents with "pleiotropic" effects provide a more effective approach to CV prevention In CANTOS study, patients achieving on-treatment hsCRP concentrations ≤2 mg/L had a higher benefit in terms of reduction in major CV events The anti-inflammatory activity of PCSK9 antagonists appears to be of a minimal extent.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Infarto Encefálico/prevenção & controle , Doença das Coronárias/prevenção & controle , Inflamação/tratamento farmacológico , Anticolesterolemiantes/farmacologia , Aterosclerose/sangue , Aterosclerose/complicações , Aterosclerose/imunologia , Infarto Encefálico/sangue , Infarto Encefálico/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/imunologia , HDL-Colesterol/antagonistas & inibidores , HDL-Colesterol/sangue , HDL-Colesterol/imunologia , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , VLDL-Colesterol/antagonistas & inibidores , VLDL-Colesterol/sangue , VLDL-Colesterol/imunologia , Ensaios Clínicos como Assunto , Doença das Coronárias/sangue , Doença das Coronárias/imunologia , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/sangue , Inflamação/complicações , Inflamação/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inibidores de PCSK9 , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Fatores de Risco , Resultado do Tratamento
6.
Int J Mol Sci ; 18(6)2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28608819

RESUMO

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed "exerkines") are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aterosclerose/terapia , Terapia por Exercício , Inflamação/terapia , Animais , Aterosclerose/complicações , Aterosclerose/imunologia , Aterosclerose/patologia , LDL-Colesterol/análise , LDL-Colesterol/imunologia , Terapia por Exercício/métodos , Humanos , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia
7.
PLoS One ; 11(2): e0148210, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26840480

RESUMO

We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL) subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC). LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA) levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high-performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months) on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation) were investigated in 11 patients with confirmed coronary artery disease (CAD). We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL-IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL-apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known beneficial effects of this drug in the treatment of atherosclerosis.


Assuntos
Complexo Antígeno-Anticorpo/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Reestenose Coronária/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Sinvastatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo Antígeno-Anticorpo/imunologia , Apolipoproteínas B/sangue , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Doença da Artéria Coronariana/sangue , Reestenose Coronária/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue
8.
Arterioscler Thromb Vasc Biol ; 35(7): 1704-11, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25953646

RESUMO

OBJECTIVE: To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL). APPROACH AND RESULTS: We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; P<0.001) and Lp(a) (R=-0.48; P<0.001) and OxPL-apoB was modestly correlated with Lp(a) (ρ=0.57; P<0.0001). The correlation in major apo(a) isoform size was concordant (R=1.0; P<0.001) among monozygotic twins but not dizygotic twins (R=0.40; P=0.055). Lp(a) and OxPL-apoB shared genetic codetermination (genetic covariance, ρG=0.774±0.032; P=1.09×10(-38)), although not environmental determination (environmental covariance, ρE=0.081±0.15; P=0.15). In contrast, Lp(a) shared environmental but not genetic codetermination with autoantibodies to malondialdehyde-modified low-density lipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a). CONCLUSIONS: OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Lipoproteínas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo Antígeno-Anticorpo/sangue , Apolipoproteínas B/sangue , Apolipoproteínas B/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Oxirredução , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/imunologia , Fosfolipídeos/sangue , Fatores de Risco , Adulto Jovem
9.
Comput Math Methods Med ; 2015: 164035, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25883675

RESUMO

Atherosclerosis, the formation of life-threatening plaques in blood vessels, is a form of cardiovascular disease. In this paper, we analyze a simplified model of plaque growth to derive physically meaningful results about the growth of plaques. In particular, the main results of this paper are two conditions, which express that the immune response increases as LDL cholesterol levels increase and that diffusion prevails over inflammation in a healthy artery.


Assuntos
Aterosclerose/fisiopatologia , Placa Aterosclerótica/fisiopatologia , Algoritmos , Artérias/patologia , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Simulação por Computador , Humanos , Inflamação/patologia , Macrófagos/metabolismo , Informática Médica/métodos , Modelos Teóricos , Fagocitose , Placa Aterosclerótica/diagnóstico
10.
PLoS One ; 10(4): e0121516, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25875611

RESUMO

OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs), as well as up-regulation of CD36, chemokine receptors and proinflammatory factors through CD36-dependent pathways and that this is associated with accelerated atherosclerosis in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). APPROACH AND RESULTS: We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT) thickness were measured by ultrasonography. Monocyte classification and MMP analysis were performed by flow cytometry. Monocyte expression of genes involved in atherosclerosis was determined by quantitative PCR. IMT and oxLDL-C were increased in FH subjects, especially in the presence of ATX. In addition, FH subjects had elevated proportions of intermediate CD14++CD16+ monocytes and higher circulating MMP levels. Stepwise linear regression identified oxLDL-C, gender and intermediate monocytes as predictors of MMPs. Monocyte expression of pro-atherogenic and pro-inflammatory genes regulated by oxLDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. CONCLUSIONS: Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly in the presence of ATX, by inducing pro-inflammatory monocytes and increased release of MMPs along with elevated monocyte expression of oxLDL-C-induced atherosclerosis-related genes.


Assuntos
Aterosclerose/complicações , Aterosclerose/imunologia , LDL-Colesterol/imunologia , Hipercolesterolemia/complicações , Hipercolesterolemia/imunologia , Lipoproteínas LDL/imunologia , Monócitos/imunologia , Adulto , Aterosclerose/genética , Aterosclerose/patologia , Antígenos CD36/genética , Antígenos CD36/imunologia , Espessura Intima-Media Carotídea , Micropartículas Derivadas de Células/imunologia , Micropartículas Derivadas de Células/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Estresse Oxidativo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/imunologia
11.
Curr Opin Immunol ; 30: 91-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25282339

RESUMO

Cell death cannot go unnoticed. It demands that the surrounding cells clear away the corpses in a manner appropriate to the type of cell death. Dying cells represent a threat to the body that should be eliminated by the host immune response. Inflammasome activation followed by IL-1alpha release and IL-1beta maturation is crucial for tackling pathological conditions, including infections, whereas inflammasome activation precedes inflammatory pyroptotic cell death. On the other hand, recent studies have shown that the inflammasome plays an important role in the pathogenesis of metabolic diseases, including obesity, diabetes, and atherosclerosis. Here, we review current knowledge of the association between cell death, excess metabolites, and inflammasome activation as it relates to chronic inflammatory diseases.


Assuntos
Inflamassomos/imunologia , Animais , Aterosclerose/imunologia , Morte Celular , LDL-Colesterol/imunologia , Gota/imunologia , Humanos , Síndrome de Lise Tumoral/imunologia
12.
J Immunol ; 193(2): 817-26, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24935924

RESUMO

Scavenger receptor class B type I (SR-BI)-deficient mice display reduced survival to endotoxic shock and sepsis. The understanding of the mechanisms underlying SR-BI protection has been hampered by the large spectrum of SR-BI functions and ligands. It notably plays an important role in the liver in high-density lipoprotein metabolism, but it is also thought to participate in innate immunity as a pattern recognition receptor for bacterial endotoxins, such as LPS. In this study, we sought to determine the tissue-specific contribution of SR-BI in the hyperinflammatory response and high mortality rates observed in SR-BI(-/-) mice in endotoxicosis or sepsis. Restoring plasma levels of high-density lipoprotein, which are critical lipoproteins for LPS neutralization, did not improve acute outcomes of LPS injection in SR-BI(-/-) mice. Mice deficient for SR-BI in hepatocytes, endothelial cells, or myeloid cells were not more susceptible to LPS-induced death. However, if SR-BI ablation in hepatocytes led to a moderate increase in systemic inflammatory markers, SR-BI deficiency in myeloid cells was associated with an anti-inflammatory effect. Finally, mice deficient for SR-BI in the adrenal cortex, where the receptor provides lipoprotein-derived cholesterol, had impaired secretion of glucocorticoids in response to stress. When exposed to an endotoxin challenge, these mice exhibited an exacerbated systemic and local inflammatory response, reduced activation of atrophy genes in muscle, and high lethality rate. Furthermore, polymicrobial sepsis induced by cecal ligature and puncture resulted in early death of these animals. Our study clearly demonstrates that corticoadrenal SR-BI is a critical element of the hypothalamic-pituitary-adrenal axis to provide effective glucocorticoid-dependent host defense after an endotoxic shock or bacterial infection.


Assuntos
Córtex Suprarrenal/imunologia , Lipopolissacarídeos/imunologia , Receptores Depuradores Classe B/imunologia , Sepse/imunologia , Choque Séptico/imunologia , Córtex Suprarrenal/metabolismo , Animais , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , LDL-Colesterol/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/imunologia , Hepatócitos/metabolismo , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Células Mieloides/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptores Depuradores Classe B/deficiência , Receptores Depuradores Classe B/genética , Sepse/microbiologia , Sepse/mortalidade , Choque Séptico/microbiologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Análise de Sobrevida , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
13.
Curr Vasc Pharmacol ; 12(3): 518-26, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23092412

RESUMO

The impact on cardiovascular events achieved by statin therapy seems to be mostly attributable to their cholesterol- lowering effect, with a highly debated contribution of the lipid-independent pleiotropic effects. Statins have an established role in the treatment of hypercholesterolemia with a clear and robust reduction in cardiovascular morbidity and mortality. Nevertheless, the pathophysiologic effect of statins on inflammatory responses and local atherosclerotic plaque morphology in humans remains a matter of debate. In particular, the question remains whether statin-induced alterations in plaque composition can be ascribed mainly to low density lipoprotein cholesterol (LDL-C) lowering or an antiinflammatory pleiotropic effect, or both. This review summarizes the available evidence of the effects of statins on carotid plaque cellular composition in clinical settings, focusing on lipid-related and lipid-independent effects of statin therapy. A systematic review of the web online databases was performed. Studies in humans evaluating the effect of statins on composition of carotid plaque removed at endarterectomy were eligible for inclusion. Data support the view that plaque composition even after a short-term lipid lowering therapy is significantly modulated by the degree of LDL-C lowering. A contribution of LDL-C independent, anti-inflammatory mechanisms of statins on plaque stability is only suggested by some of the studies. Actually, data strongly support the current guidelines based on progressively lower LDL-C targets depending upon the cardiovascular risk of individual patients.


Assuntos
Doenças das Artérias Carótidas/tratamento farmacológico , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Animais , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/imunologia , LDL-Colesterol/imunologia , Ensaios Clínicos como Assunto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/imunologia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Placa Aterosclerótica/imunologia
15.
Cardiovasc Drugs Ther ; 26(4): 293-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22441892

RESUMO

PURPOSE: To assess the difference in the prevalence of invariant Natural Killer T (iNKT) lymphocytes between hyperlipidemic and control individuals and to evaluate changes in iNKT cell levels after 6 months lipid lowering therapy. METHODS: A total of 77 hyperlipidemic individuals (54 ± 5 years) were assigned to simvastatin 40 mg or ezetimibe 10 mg daily for 6 months. Fifty individuals with normal cholesterol levels were used as control. iNKT cells were measured by flow cytometry in peripheral blood. RESULTS: Patients with hypercholesterolemia had significantly lower iNKT cell levels (percentage on the lymphocyte population) compared to control group (0.16 ± 0.04% vs 0.39 ± 0.08%, p = 0.03). iNKT cells significantly increased after 6 months treatment with simvastatin (from 0.15 ± 0.04% to 0.28 ± 0.11%, p = 0.03) but not with ezetimibe (from 0.16 ± 0.05% to 0.17 ± 0.06%, p = 0.55). Simvastatin treatment did not alter the activation status of iNKT cells as measured by HLA-DR expression. Changes of iNKT cells were independent from changes in total (r(2) = 0.009, p = 0.76) or LDL cholesterol (r(2) = 0.008, p = 0.78) reached by simvastatin. CONCLUSIONS: Hyperlipidemic patients have reduced numbers of iNKT in peripheral circulation compared to individuals with normal cholesterol levels. Their number is increasing after long term administration of simvastatin 40 mg but not after ezetimibe.


Assuntos
Anticolesterolemiantes/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/imunologia , Imunomodulação/efeitos dos fármacos , Células T Matadoras Naturais/imunologia , Anticolesterolemiantes/imunologia , Azetidinas/imunologia , Azetidinas/farmacologia , HDL-Colesterol/sangue , HDL-Colesterol/imunologia , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Ezetimiba , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/imunologia , Hiperlipidemias/sangue , Imunomodulação/imunologia , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/efeitos dos fármacos , Prevalência , Sinvastatina/imunologia , Sinvastatina/farmacologia , Triglicerídeos/sangue , Triglicerídeos/imunologia
16.
Int J Food Sci Nutr ; 63(1): 36-40, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21707451

RESUMO

To investigate the effect of n-3 polyunsaturated fatty acid (PUFA) supplementation on the fatty acid composition of erythrocyte phospholipids and breast milk lipids, pregnant Brazilian women in the 30th week of gestation were randomized to supplement their usual diet with 2 g/day of fish oil (FO group) or primrose oil (PO group, control) capsules for 15 days. Erythrocyte phospholipids from FO group had proportionally higher docosahexaenoicacid and eicosapentaenoic acid levels and furthermore, the ratio of n-6/n-3 PUFA was significantly lower in the breast milk lipids compared with the control group. Assessment of plasma anti-oxLDL autoantibodies and thiobarbituric acid-reactive substance concentration demonstrated that both groups had the same levels and they were unaltered by supplementations.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Linoleicos/farmacologia , Leite Humano/metabolismo , Fosfolipídeos/sangue , Óleos de Plantas/farmacologia , Gravidez/metabolismo , Ácido gama-Linolênico/farmacologia , Adulto , Autoanticorpos/sangue , Brasil , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Dieta , Gorduras na Dieta/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacologia , Eritrócitos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Feminino , Humanos , Ácidos Linoleicos/metabolismo , Oenothera biennis , Óleos de Plantas/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Adulto Jovem , Ácido gama-Linolênico/metabolismo
17.
Endokrynol Pol ; 62(5): 421-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22069103

RESUMO

BACKGROUND: Thyroid autoimmunity has been suggested as a risk factor for atherosclerosis independent of thyroid function in several studies. The aim of this study was to investigate whether thyroid autoimmunity had any effect on hyperlipidaemia, obesity and abdominal obesity independent of thyroid function. MATERIAL AND METHODS: 184 premenopausal female patients with Hashimoto's thyroiditis (HT) and 150 healthy premenopausal female volunteers as control group (CG) were included in the study. According to thyroid function status, the patients were divided into three subgroups: overt hypothyroid patients (ohp), subclinical hypothyroid patients (shp) and euthyroid patients (ep). Body mass index (BMI), waist to hip ratios, waist circumference (WC), and serum lipid levels of all the participants were determined. These parameters of ep were compared with those of ohp, shp and CG. Relationships among thyroid stimulating hormone (TSH), thyroid autoantibodies and lipid levels were investigated. RESULTS: There were no significant differences between serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels of ohp and ep with HT (P = 0.18, P = 0.07 respectively) and LDL-C levels of ep were higher than those of CG (P = 0.03, P = 0.042, respectively). Although TSH levels did not correlate with serum lipid levels, levels of anti-thyroid peroxidase antibody correlated with triglyceride levels and WCs (r = 0.158; P = 0.013, r = 0.128; P = 0.048 respectively) and negatively correlated with high density lipoprotein cholesterol (HDL-C) levels (r = -0.137; P = 0.031). Levels of anti-thyroglobulin antibody also correlated with triglyceride and nonHDL-C levels (r = 0.208; P = 0.007, r = 0.158; P = 0.043 respectively). CONCLUSION: Thyroid autoimmunity may have some effects on hyperlipidaemia and abdominal obesity independent of thyroid function.


Assuntos
Autoimunidade/fisiologia , Doença de Hashimoto/imunologia , Hiperlipidemias/imunologia , Obesidade Abdominal/imunologia , Hormônios Tireóideos/imunologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , LDL-Colesterol/imunologia , Feminino , Humanos , Estatística como Assunto , Tireotropina/imunologia
18.
JNMA J Nepal Med Assoc ; 51(184): 157-63, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22922894

RESUMO

INTRODUCTION: Different authorities have put forward their criteria to define metabolic syndrome (MetS). The aim of this study was to find the prevalence of MetS in hypertensive individuals by the available three different definitions from National Cholesterol Education Program (NCEP), International diabetes Federation (IDF) and WHO and their association with other cardiac risk factors. METHODS: After anthropometric measurements fasting blood was analyzed for glucose, lipids, high sensitivity C-reactive protein (hsCRP) and anti-oxidized LDL antibody in 150 hypertensive individuals. A ten-year coronary heart disease risk was predicted using the Framingham risk score (FRS). RESULTS: The prevalence of MetS was 54.7 % by NCEP, 42.0 % by IDF) and 18.7 % by WHO. As many as 63.4 % had MetS by any definition, while only 9.4 % fulfilled all the criteria of the three definitions. The association of cardiac risk factors also varied according to the definition used. hsCRP was significantly elevated in MetS compared to non-MetS. Body mass index, waist circumference and HDL-C were associated in MetS defined by NCEP and IDF. FRS was higher in MetS defined by Adult Treatment Panel and WHO definitions. An increase in urine albumin and a decrease in eGFR were associated with MetS individuals defined by WHO only. CONCLUSION: There is a wide variation in the prevalence of MetS and associated cardiac risk factors according to three different definitions used. The different cardiac risk factors among MetS also vary with the definitions used. However, hsCRP and emerging risk factor are significantly elevated in hypertensive individuals with MetS as defined by all definitions.


Assuntos
Biomarcadores/sangue , Pressão Sanguínea , Hipertensão/epidemiologia , Síndrome Metabólica/complicações , Medição de Risco/métodos , Adulto , Idoso , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/imunologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Nepal/epidemiologia , Prevalência , Prognóstico , Fatores de Risco
19.
Bull Math Biol ; 72(6): 1534-61, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20440571

RESUMO

Atherosclerosis is a chronic disease of the large arteries, characterized by fatty cholesterol-filled streaks and plaque build-up within the artery wall. Within the past decade, inflammation has been determined as a crucial factor in all stages of lesion formation, however, many of the mechanisms involved are not yet fully understood. We present a simplified ODE model that explores the role of inflammation in atherosclerosis. The model incorporates two of the main lesion constituents, cholesterol-carrying modified Low Density Lipoproteins (LDLs) and macrophage foam cells. Their complex interactions are combined into general functions, and the long-term model behaviour is investigated through phase plane analysis and simulations. Our results indicate that the underlying mechanisms of macrophage uptake of modified LDL can have a deep impact on the cellular dynamics in the lesion. Our model demonstrates that it is macrophage proliferation and constant signalling to the endothelial cells, rather than an increasing influx of modified LDL, that drives lesion instability.


Assuntos
Aterosclerose/etiologia , Inflamação/etiologia , Modelos Biológicos , Aterosclerose/imunologia , Proliferação de Células , LDL-Colesterol/imunologia , Doença Crônica , Simulação por Computador , Células Espumosas/imunologia , Humanos , Inflamação/imunologia , Linfócitos T/imunologia , Túnica Íntima/imunologia
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