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3.
Expert Opin Pharmacother ; 21(14): 1675-1684, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32646313

RESUMO

INTRODUCTION: Severe hypertriglyceridemia (sHTG) is a complex disorder of lipid metabolism characterized by plasma levels of triglyceride (TG) greater than 885 mg/dl (>10 mmol/L). The treatment of sHTG syndromes is challenging because conventional treatments are often ineffective in reducing TG under the threshold to prevent acute pancreatitis (AP). The inhibition of APOC3, which encodes a protein involved in triglyceride (TG)-rich lipoproteins (TGRLs) removal, has been reported to be a novel target for the treatment of sHTG. Volanesorsen is a second-generation antisense oligonucleotide inhibiting apoC-III transcription/translation that has been recently approved in Europe for Familial Chylomicronemia Syndrome (FCS) treatment. AREAS COVERED: This review summarizes the evidences on the efficacy and safety of volanesorsen for the treatment of sHTG syndromes. EXPERT OPINION: Volanesorsen effectively reduces TG in sHTG through a mechanism that is mainly LPL-independent, potentially decreasing the risk of AP. Some safety concerns have been raised with the use of volanesorsen, mainly represented by the occurrence of thrombocytopenia. Due to the potential severity of side effects, some caution is needed before affirming the long-term utility of this drug. Despite this, volanesorsen currently remains the only drug that has been demonstrated effective in FCS, which otherwise remains an untreatable disease.


Assuntos
Apolipoproteína C-III/antagonistas & inibidores , Hipertrigliceridemia/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos/uso terapêutico , Europa (Continente) , Humanos , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Hipertrigliceridemia/sangue , Hipertrigliceridemia/metabolismo , Lipoproteínas/sangue , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/efeitos adversos , Pancreatite/induzido quimicamente , Pancreatite/prevenção & controle , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Triglicerídeos/sangue
4.
Medicine (Baltimore) ; 99(20): e20178, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443336

RESUMO

BACKGROUND: The objective of this study is to examine the association between serum lipoprotein levels (SLL) and cognitive impairment (CI) in patients with acute cerebral infarction (ACI). METHODS: All published studies will be searched from the following electronic databases: PubMed, EMBASE, Cochrane Library, PsycINFO, Web of Science, WANGFANG, and China National Knowledge Infrastructure from inauguration of each electronic database up to March 1, 2020. In addition, we will also search other sources, such as dissertations, Google scholar, conference proceedings, and reference lists of relevant reviews. We will not apply any language restrictions to the electronic databases. Two researchers will independently carry out literature selection, data collection, and methodological quality. A third researcher will help to solve any divergences by discussion. The RevMan 5.3 software will be employed to pool the collected data and to analyze the outcome data. RESULTS: This study will scrutinize the association between SLL and CI in patients with ACI. CONCLUSIONS: The results of this study will present helpful evidence of the association between SLL and CI in patients with ACI.Registration number: INPLASY202040018.


Assuntos
Isquemia Encefálica/patologia , Infarto Cerebral/complicações , Disfunção Cognitiva/etiologia , Lipoproteínas/sangue , Doença Aguda , Infarto Cerebral/epidemiologia , China/epidemiologia , Disfunção Cognitiva/sangue , Feminino , Humanos , Masculino , Sensibilidade e Especificidade
5.
Medicine (Baltimore) ; 99(20): e20258, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443365

RESUMO

BACKGROUND: The target of this study is to summarize the association between the serum lipoprotein levels and neurological function in patients with acute ischemic stroke. METHODS: A comprehensive search of Cochrane Library, PUBMED, EMBASE, Web of Science, and Chinese Biomedical Literature Database, China National Knowledge Infrastructure from inception to the February 29, 2020 without language and publication date restrictions. All searched studies will be selected by 2 authors independently against the eligibility criteria. Included studies will be critically appraised, and essential data will be extracted by 2 independent authors. If necessary, meta-analysis will be utilized to synthesize the outcome data from included articles. If it is not possible, a narrative synthesis will be undertaken. RESULTS: This study will summarize the up-to-date evidence to investigate the association between serum lipoprotein levels and neurological function in patients with acute ischemic stroke. CONCLUSION: Its results may present beneficial evidence and guidance for the clinical practice and further studies. STUDY REGISTRATION NUMBER: INPLASY202040043.


Assuntos
Isquemia Encefálica/complicações , Lipoproteínas/sangue , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/etiologia , Acidente Vascular Cerebral/complicações , Estudos de Casos e Controles , Humanos , Projetos de Pesquisa
6.
Lipids Health Dis ; 19(1): 44, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178671

RESUMO

BACKGROUND AND AIMS: It has been confirmed that remnant-like particle cholesterol (RLP-C) mediates the progression of coronary artery disease (CAD). Currently there is limited information on RLP-C in menopausal women. With the special status of diabetes mellitus (DM) combined with the special body changes of the menopausal women, the RLP-C is particularly important when studying the changes that occurred in response to CAD and its associated risk factors. This study discussed whether RLP-C could be an independent risk factor for menopausal women with CAD and DM. METHODS: The cohort consisted of 4753 menopausal women who had undergone coronary angiography. Subjects were separated into CAD and non-CAD groups, and univariate and multivariate logistic regression analysis of CAD risk factors were performed. All patients with a history of DM were divided into DM subgroups. Then, the univariate and multivariate logistic regression analysis of the risk factors of CAD and the comparison among age groups in the DM subgroup were performed. After age stratification of the DM group, the Kruskal-Wallis test was used to analyze the differences of various lipid indexes among age groups. RESULTS: The multivariate logistic regression showed that RLP-C was an independent risk factor for CAD in menopausal women (OR 1.232, 95%CI 1.070-1.419). In the DM subgroup, it was also found that RLP-C was an independent risk factor for CAD (OR 1.366, 95%CI 1.043-1.791). Kruskal-Wallis test analysis found that RLP-C had no significant difference among three groups (P > 0.05). CONCLUSIONS: RLP-C was proved to be an independent risk factor for menopausal women with CAD and DM.


Assuntos
Doença da Artéria Coronariana/sangue , Diabetes Mellitus/sangue , Menopausa/sangue , Idoso , China , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Lipoproteínas/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Software , Triglicerídeos/sangue
7.
Sci Rep ; 10(1): 4160, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139762

RESUMO

Physical inactivity has emerged as an important cardiometabolic risk factor; however, the beneficial impacts of physical exercise according physical fitness status are still unclear. To analyze the lipoproteins and immune-endocrine response to acute aerobic exercise sessions performed at different intensities according physical fitness status and evaluated the gene expression in monocyte cells. Twelve individuals, divided into Low and High VO2max, performed three randomized acute exercise sessions at low (<60% VO2max), moderate (60-75% VO2max), and high (>90% VO2max) intensities. Blood samples were collected pre, immediately post, and 60 minutes post-exercise to analyze NEFA, triacylglycerol, non-HDL-c, HDL-c, PAI-1, leptin and adiponectin concentrations. Blood samples were collected from another set of twelve individuals for use in monocyte cell cultures to analyze L-CAT, CETP, and AMPK gene expressions. Low VO2max group pre-exercise exhibited higher postprandial leptin and total cholesterol concentrations than High VO2max group (p < 0.05). Exercise performed in high-intensity promoted a decreased leptin and NEFA levels (p < 0.05, for both), but for PAI-1 levels was decreased (p < 0.05) only for the Low VO2max group. Triacylglycerol levels decreased after all exercise sessions (p < 0.05) for both groups, and HDL-c exhibited decrease during moderate-intensity (p < 0.05), but this scenario was attenuated in Low VO2max group. Low VO2max individuals exhibit some metabolic-endocrine disruption, and acute aerobic exercise sessions performed at low, moderate, and high intensities are capable of modulating metabolic-endocrine parameters, mainly at high-intensity, in a physical fitness-dependent way, given that Low VO2max group was more responsive and seem to be able to appropriate more exercise-related benefits.


Assuntos
Exercício Físico/fisiologia , Lipoproteínas/sangue , Lipoproteínas/metabolismo , Adulto , Feminino , Hematócrito , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Consumo de Oxigênio , Aptidão Física/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Triglicerídeos/sangue
8.
PLoS Genet ; 16(3): e1008605, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32150548

RESUMO

Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). Here we studied, association of rare variants and 226 serum lipoproteins, lipids and amino acids in 7,142 (discovery plus follow-up) healthy participants. We leveraged the information from multiple metabolite measurements on the same participants to improve discovery in rare variant association analyses for gene-based and gene-set tests by incorporating correlated metabolites as covariates in the validation stage. Gene-based analysis corrected for the effective number of tests performed, confirmed established associations at APOB, APOC3, PAH, HAL and PCSK (p<1.32x10-7) and identified novel gene-trait associations at a lower stringency threshold with ACSL1, MYCN, FBXO36 and B4GALNT3 (p<2.5x10-6). Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene-set analyses also corrected for effective number of tests, with IDL and LDL parameters, as well as circulating cholesterol (pMETASKAT<2.41x10-6). In conclusion, using an approach that leverages metabolite measurements obtained in the same participants, we identified novel loci and pathways involved in the regulation of these important metabolic biomarkers. As large-scale biobanks continue to amass sequencing and phenotypic information, analytical approaches such as ours will be useful to fully exploit the copious amounts of biological data generated in these efforts.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Variação Genética/genética , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Lipoproteínas/sangue , Masculino , Fenótipo , Triglicerídeos/sangue
9.
Medicine (Baltimore) ; 99(13): e19665, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221094

RESUMO

The aim of this study was to investigate the relationship between blood lipid level and the parameters of embryo morphology of in vitro fertilization (IVF).A total of 488 patients undergoing conventional IVF were divided into pregnant (n = 286) and nonpregnant (n = 202) groups. Levels of triglycerides (TG), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoprotein (LDL), lipoprotein (a), lipoprotein (b), and embryo outcomes were studied. Spearman correlation was performed to analyze the correlation between blood lipid levels and embryo quality in pregnant group.The normal fertilization rate and number of good quality embryos were higher than nonpregnant group (P < .05). TG, TC, and LDL levels were negatively correlated with number of normal fertilized oocytes, while TG, TC, and Lp(b) were negatively correlated with number of good quality embryos. TG level was negatively correlated with number of oocytes and cleavage embryos while HDL and Lp(a) were positively correlated with number of oocytes, normal fertilized oocytes and cleavage embryos (P < .05).TG, TC, LDL, and Lp(b) levels had negative correlation with embryo quality, while HDL and Lp(a) had positive correlation with the embryo quality. Our present findings showed blood lipid levels may provide certain reference for the prediction of IVF pregnancy outcome.


Assuntos
Embrião de Mamíferos/citologia , Fertilização In Vitro/métodos , Lipídeos/sangue , Adulto , Índice de Massa Corporal , Feminino , Humanos , Lipoproteínas/sangue , Oócitos/citologia , Triglicerídeos/sangue
10.
Artigo em Inglês | MEDLINE | ID: mdl-32151767

RESUMO

Loss-of-function (LOF) mutations in ANGPTL3, an inhibitor of lipoprotein lipase (LPL), cause a drastic reduction of serum lipoproteins and protect against the development of atherosclerotic cardiovascular disease. Therefore, ANGPTL3 is a promising therapy target. We characterized the impacts of ANGPTL3 depletion on the immortalized human hepatocyte (IHH) transcriptome, lipidome and human plasma lipoprotein lipidome. The transcriptome of ANGPTL3 knock-down (KD) cells showed altered expression of several pathways related to lipid metabolism. Accordingly, ANGPTL3 depleted IHH displayed changes in cellular overall fatty acid (FA) composition and in the lipid species composition of several lipid classes, characterized by abundant n-6 and n-3 polyunsaturated FAs (PUFAs). This PUFA increase coincided with an elevation of lipid mediators, among which there were species relevant for resolution of inflammation, protection from lipotoxic and hypoxia-induced ER stress, hepatic steatosis and insulin resistance or for the recovery from cardiovascular events. Cholesterol esters were markedly reduced in ANGPTL3 KD IHH, coinciding with suppression of the SOAT1 mRNA and protein. ANGPTL3 LOF caused alterations in plasma lipoprotein FA and lipid species composition. All lipoprotein fractions of the ANGPTL3 LOF subjects displayed a marked drop of 18:2n-6, while several highly unsaturated triacylglycerol (TAG) species were enriched. The present work reveals distinct impacts of ANGPTL3 depletion on the hepatocellular lipidome, transcriptome and lipid mediators, as well as on the lipidome of lipoproteins isolated from plasma of ANGPTL3-deficient human subjects. It is important to consider these lipidomics and transcriptomics findings when targeting ANGPTL3 for therapy and translating it to the human context.


Assuntos
Proteínas Semelhantes a Angiopoietina/metabolismo , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas/metabolismo , Mutação com Perda de Função , Adulto , Idoso , Proteínas Semelhantes a Angiopoietina/genética , Linhagem Celular , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/metabolismo
11.
Nutrients ; 12(2)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033078

RESUMO

Soda consumption in adolescents has been linked to poorer metabolic outcomes. We tested whether replacing soda with reduced fat milk would improve features of atherogenic dyslipidemia and other cardiometabolic risk factors. Thirty overweight and obese adolescent boys who were habitual consumers of sugar-sweetened beverages were randomly assigned to consume 24 oz/day of sugar-sweetened soda or an energy equivalent of reduced fat (2%) milk for 3 weeks with crossover to the alternate beverage after a ≥ 2 weeks washout. Plasma lipids and lipoproteins and other laboratory measures were assessed after each beverage period. Lipid and lipoprotein measurements, C-reactive protein, and serum transaminases did not differ significantly between the soda and milk phases of the study. Systolic blood pressure z-score and uric acid concentration were significantly lower after consuming milk compared to soda. Milk consumption also significantly decreased plasma glucosyl ceramide (d18:1/C16:0) and lactosylceramides (d18:1/C16:0 and d18:1/C18:0). While no effects of replacing soda with milk on lipid and lipoprotein measurements were observed in these normolipidemic weight-stable adolescent boys, decreases in systolic blood pressure, uric acid, and glycosphingolipids suggest that an overall favorable effect on cardiometabolic risk can be achieved following a short-term dietary intervention.


Assuntos
Bebidas Gaseificadas/efeitos adversos , Ingestão de Líquidos/fisiologia , Leite , Obesidade Pediátrica/dietoterapia , Bebidas Adoçadas com Açúcar/efeitos adversos , Adolescente , Animais , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/dietoterapia , Dislipidemias/etiologia , Glucosilceramidas/sangue , Humanos , Lactosilceramidas/sangue , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Obesidade Pediátrica/complicações , Ácido Úrico/sangue
12.
Curr Opin Endocrinol Diabetes Obes ; 27(2): 104-109, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32011347

RESUMO

PURPOSE OF REVIEW: The speed of removal from the plasma of apolipoprotein B-containing lipoproteins, for example, chylomicrons, VLDL and LDL is determinant of the plasma concentration of these lipoproteins, is influenced by genetic features and ambient factors, and has implications in atherogenesis. As aging increases the clinical complications of atherosclerosis, it is important to appraise the status of the removal mechanisms in elderly individuals. RECENT FINDINGS: Removal of triglyceride-rich lipoproteins remnants is delayed but the triglyceride breakdown is unchanged in elderly individuals. The discovery of PCSK9, enzyme that degrades LDL receptors, and the recent observation that PCSK9 is elevated in the elderly raises another hypothesis to account for the increased LDL-cholesterol levels in the elderly. The removal of cholesterol from cells by HDL, the first step of cholesterol reverse transport is also less efficient in the elderly, which may compromise the body cholesterol homeostasis. SUMMARY: Aging determines reduction of the efficiency of lipoprotein plasma removal mechanisms, which is implicated in increased incidence of cardia complications. Moreover, aging is frequently accompanied by physical activity reduction, weight gain, and metabolic disturbances that can further decrease the efficacy of the removal mechanisms. This knowledge is important for promoting cardiovascular health in the elderly and prolonging survival.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/etiologia , Metabolismo dos Lipídeos/fisiologia , Lipoproteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas B/sangue , Aterosclerose/etiologia , Aterosclerose/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Colesterol/sangue , Humanos , Lipoproteínas/sangue , Lipoproteínas LDL/sangue , Fatores de Risco
13.
BMC Neurol ; 20(1): 47, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033596

RESUMO

BACKGROUND: It is unclear whether non-high-density lipoprotein cholesterol (Non-HDL-C) is associated with haemorrhagic transformation (HT) after acute ischaemic stroke (AIS). We aimed to explore the association between Non-HDL-C and HT, as well as compare the predictive values of Non-HDL-C and low-density lipoprotein cholesterol (LDL-C) for HT. METHODS: We consecutively enrolled AIS patients within 7 days of stroke onset. Participants were divided into four categories according to quartiles of Non-HDL-C. HT was assessed by follow-up brain imaging. We assessed the association between Non-HDL-C, LDL-C and HT in multivariate logistic regression analysis. RESULTS: A total of 2043 patients were included, among whom 232 were identified as HT. Compared with the highest quartiles, the first, second and third quartiles of Non-HDL-C were associated with increased risk of HT (adjusted odds ratios [ORs] 1.74 [95% confidence interval [CI] 1.09-2.78], 2.01[95% CI 1.26-3.20], and 1.76 [95% CI 1.10-2.83], respectively, P for trend = 0.024). Similar results were found for LDL-C. There was significant interaction between Non-HDL-C and age (P for interaction = 0.021). The addition of Non-HDL-C and LDL-C to conventional factors significantly improved predictive values [Non-HDL-C, net reclassification index (NRI) 0.24, 95%CI 0.17-0.31, P < 0.001; LDL-C, NRI 0.15, 95%CI 0.08-0.22, P = 0.03]. CONCLUSIONS: Low Non-HDL-C was associated with increased risks of HT. In addition, Non-HDL-C has similar effects as LDL-C for predicting HT.


Assuntos
Isquemia Encefálica/complicações , LDL-Colesterol/sangue , Colesterol/sangue , Lipoproteínas/sangue , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Ann Biol Clin (Paris) ; 78(1): 17-26, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108576

RESUMO

The lipoproteinogram (or lipidogram) consists in an electrophoretic separation of the main classes of serum lipoproteins. Separation was done in agarose gel using the Sebia Hydragel Lipo + Lp(a)® kit. A repeatability study (n=6) was conducted on 3 sera (1 normolipidemic, 1 hypertriglyceridemic and 1 with a high Lp(a) concentration). The reproducibility was studied on these 3 sera and on an ascites liquid containing chylomicrons, upon 6 days (n=6). A quantitative approach was made by studying areas under the curve and percentages of fractions. In both cases (repeatability and reproducibility), the revelation of the lipoproteins in the gel after electrophoretic migration was made either by staining with Sudan Black (procedure recommended by Sebia), or with Fat Red 7B. Regardless of staining, both repeatability and reproducibility studies show that all lipoprotein fractions were correctly detected at their respective positions, leading to satisfactory interpretations of lipoproteinograms. Our reproducibility study also confirmed a good stability of the fractions over 6 days (storage at +5 ± 3̊C). In addition, the Fat Red 7B staining leads to a shorter technical time (about 40 min) for the gel drying and staining/destaining phases, which allows us to respond more quickly to certain urgent requests such as chylothorax diagnosis.


Assuntos
Compostos Azo/farmacologia , Eletroforese/métodos , Lipoproteínas/análise , Lipoproteínas/sangue , Kit de Reagentes para Diagnóstico , Coloração e Rotulagem/métodos , Líquido Ascítico/química , Compostos Azo/química , Análise Química do Sangue/métodos , Fracionamento Químico/métodos , Eletroforese em Gel de Ágar , Humanos , Lipoproteína(a)/análise , Lipoproteína(a)/sangue , Reprodutibilidade dos Testes
15.
PLoS One ; 15(1): e0228004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990936

RESUMO

Type 2 diabetes and dyslipidemia are diseases that collectively increase the risk of patients developing cardiovascular complications. Several incretin-based drugs are reported to improve lipid metabolism, and one of these medications, anagliptin, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been shown to decrease serum triglyceride and low-density lipoproteins cholesterol. This study aimed to conduct an investigation into the effects of anagliptin on serum lipid profiles. This multicenter, open-label, randomized (1:1), parallel group study was designed to evaluate the effects of anagliptin on serum lipid profiles (triglycerides, lipoproteins, apolipoproteins, and cholesterol fractions). The study involved 24 patients with type 2 diabetes at two participating hospitals for a period of 24 weeks. Patients were randomly assigned to the anagliptin (n = 12) or control (n = 12) groups. Patients in the anagliptin group were treated with 200 mg of the drug twice daily. Patients in the control group did not receive anagliptin, but continued with their previous treatment schedules. Lipid metabolism was examined under fasting conditions at baseline and 24 weeks. Patients treated with anagliptin for 24 weeks exhibited significantly reduced levels of serum apolipoprotein B-48, a marker for lipid transport from the intestine, compared with the control group patients (P < 0.05). After 24 weeks of treatment, serum adiponectin levels were significantly raised, whereas glycated hemoglobin (HbA1c) levels were significantly lower compared with the baseline in the anagliptin group (P < 0.05), but not in the control group. This study showed that the DPP-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels, suggesting that this drug may have beneficial effects on lipid metabolism possibly mediated by the inhibition of intestinal lipid transport.


Assuntos
Apolipoproteína B-48/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Pirimidinas/uso terapêutico , Adiponectina/sangue , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Jejum/sangue , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
16.
Environ Health ; 19(1): 5, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931806

RESUMO

BACKGROUND: The associations of perfluoroalkyl substance (PFAS) exposure with blood lipids and lipoproteins are inconsistent, and existing studies did not account for metabolic heterogeneity of lipoprotein subspecies. This study aimed to examine the associations between plasma PFAS concentrations and lipoprotein and apolipoprotein subspecies. METHODS: The study included 326 men and women from the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) Lost randomized trial. Five PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), were measured in plasma at baseline. For lipoprotein and apolipoprotein subspecies, total plasma was fractionated first by apolipoprotein (apo) C-III content and then by density. Each subfraction was then measured for apoB, apoC-III, and apoE concentrations, as well as triglyceride and cholesterol contents, both at baseline and at 2 years. RESULTS: For lipids and apolipoproteins in total plasma at baseline, elevated plasma PFAS concentrations were significantly associated with higher apoB and apoC-III concentrations, but not with total cholesterol or triglycerides. After multivariate adjustment of lifestyle factors, lipid-lowering medication use, and dietary intervention groups, PFAS concentrations were primarily associated with lipids or apolipoprotein concentrations in intermediate-to-low density lipoprotein (IDL + LDL) and high-density lipoprotein (HDL) that contain apoC-III. Comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) were 4.16 (0.4) vs 3.47 (0.4) for apoB (P trend = 0.04), 2.03 (0.2) vs 1.66 (0.2) for apoC-III (P trend = 0.04), and 8.4 (0.8) vs 6.8 (0.8) for triglycerides (P trend = 0.03) in IDL + LDL fraction that contains apoC-III. For HDL that contains apoC-III, comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) of apoC-III were 11.9 (0.7) vs 10.4 (0.7) (P trend = 0.01). In addition, elevated PFNA and PFDA concentrations were also significantly associated with higher concentrations of apoE in HDL that contains apoC-III (P trend< 0.01). Similar patterns of associations were demonstrated between baseline PFAS concentrations and lipoprotein subspecies measured at 2 years. Baseline PFAS levels were not associated with changes in lipoprotein subspecies during the intervention. CONCLUSIONS: Our results suggest that plasma PFAS concentrations are primarily associated with blood lipids and apolipoproteins in subspecies of IDL, LDL, and HDL that contain apoC-III, which are associated with elevated cardiovascular risk in epidemiological studies. Future studies of PFAS-associated cardiovascular risk should focus on lipid subfractions.


Assuntos
Fluorcarbonetos/sangue , Lipídeos/sangue , Obesidade/sangue , Adulto , Idoso , Ácidos Alcanossulfônicos/sangue , Apolipoproteínas/sangue , Caprilatos/sangue , Ácidos Decanoicos/sangue , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Ácidos Sulfônicos/sangue
17.
Lipids Health Dis ; 19(1): 3, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901240

RESUMO

BACKGROUND: Use of ezetimibe on top of statin therapy has been shown to be effective to reduce LDL cholesterol level in hypercholesterolemic patients. However, little is known regarding the individual variety of the effectiveness of ezetimibe. We hypothesized that hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene exhibit better response to ezetimibe than those without, based on the fact that ezetimibe is hyper-effective for in patients with sitosterolemia caused by ABCG5 or ABCG8 genetic mutations. METHODS: Electronical medical record were reviewed in a total of 321 hypercholesterolemic patients (baseline LDL cholesterol = 192 ± 46 mg/dl) prescribed ezetimibe 10 mg daily on top of atorvastatin 10 mg daily who had undergone genetic analysis of ABCG5 or ABCG8 gene in our institute since 2006 to 2017. Pathogenicity of the variants were determined using standard variant filtering schema, including minor allele frequency, in silico annotation tools. Patients were divided into 2 groups based on the presence of ABCG5 or ABCG8 mutation. We compared the percent reduction of LDL cholesterol as well as the achieved LDL cholesterol levels between these 2 groups. RESULTS: We found 26 (8%) individuals who exhibit deleterious mutations in ABCG5 or ABCG8 gene. Baseline characteristics under the atorvastatin 10 mg therapy were comparable in age, gender, and LDL cholesterol level between 2 groups. Under these conditions, percent reduction of LDL cholesterol in mutation positive group was significantly larger than that of mutation negative group (28 ± 16% vs. 39 ± 21%, p < 0.05). As a result, the achieved LDL cholesterol level in mutation positive group was significantly lower than that of mutation negative group (87 ± 29 mg/dl vs. 72 ± 26% mg/dl, p < 0.05). CONCLUSION: These results suggest that ezetimibe-atorvastatin combination therapy might be more beneficial in hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene.


Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Combinação de Medicamentos , Hipercolesterolemia/tratamento farmacológico , Lipoproteínas/genética , Idoso , Atorvastatina/administração & dosagem , LDL-Colesterol/sangue , Ezetimiba/administração & dosagem , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Mutação/genética
18.
Heart Fail Clin ; 16(1): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735307

RESUMO

The effects of hyperthyroidism and hypothyroidism on the heart and cardiovascular system are well documented. It has also been shown that various forms of heart disease including but not limited to congenital, hypertensive, ischemic, cardiac surgery, and heart transplantation cause an alteration in thyroid function tests including a decrease in serum liothyronine (T3). This article discusses the basic science and clinical data that support the hypothesis that these changes pose pathophysiologic and potential novel therapeutic challenges.


Assuntos
Insuficiência Cardíaca/complicações , Doenças da Glândula Tireoide/etiologia , Hormônios Tireóideos/sangue , Biomarcadores/sangue , Ecocardiografia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Humanos , Lipoproteínas/sangue , Índice de Gravidade de Doença , Doenças da Glândula Tireoide/sangue
19.
Infect Immun ; 88(3)2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31843964

RESUMO

Lipoproteins, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9), have been shown to play a key role in the innate immune response. However, knowledge about the role and kinetics of PCSK9 in human inflammation is currently insufficient. This study aimed to investigate the interaction between inflammation and lipid metabolism, including the possible role of PCSK9. A single-blinded, placebo-controlled cross-over study using the human endotoxin model was performed. Ten healthy men received lipopolysaccharide (LPS) or placebo on two different study days after overnight fasting. Lipoproteins as well as PCSK9 were measured repetitively over 48 h. PCSK9 plasma concentrations were not induced by LPS infusion, and no correlation between PCSK9 plasma concentrations and the degree of inflammation could be identified. The observed low-density lipoprotein (LDL) response to inflammation was more complex than anticipated, especially in the very early phase after the inflammatory stimulus. Baseline concentrations of LDL, as well as high-density lipoprotein (HDL), correlated negatively with inflammatory response. Our data suggest that the lipoprotein response to inflammation is independent of PCSK9. The proposed elevations of PCSK9 and suspected correlations between PCSK9 levels and inflammatory response are not supported by our data. (This study has been registered at ClinicalTrials.gov under registration no. NCT03392701.).


Assuntos
Imunidade Inata/imunologia , Inflamação/imunologia , Lipoproteínas/sangue , Pró-Proteína Convertase 9/imunologia , Adulto , Estudos Cross-Over , Feminino , Humanos , Inflamação/sangue , Metabolismo dos Lipídeos/fisiologia , Masculino , Adulto Jovem
20.
Phytother Res ; 34(2): 239-253, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31880030

RESUMO

The aim of this systematic review and meta-analysis was to analyze the effects of grape seed extract (GSE) on glycemic control and serum lipoproteins, inflammation and body weight. Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until May 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Fifty trials were included in this meta-analysis. Pooling effect sizes from studies demonstrated a significant decrease in fasting plasma glucose (FPG) (WMD): -2.01; 95% confidence interval (CI): -3.14, -0.86), total cholesterol (TC; WMD: -6.03; 95% CI: -9.71, -2.35), low-density lipoprotein (LDL) cholesterol (WMD: -4.97; 95% CI: -8.37, -1.57), triglycerides (WMD: -6.55; 95% CI: -9.28, -3.83), and C-reactive protein (CRP) concentrations (WMD: -0.81; 95% CI: -1.25, -0.38) following GSE therapy. Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta-analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.


Assuntos
Glicemia , Peso Corporal , Extrato de Sementes de Uva/farmacologia , Inflamação/sangue , Lipoproteínas/sangue , Proteína C-Reativa/análise , Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
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