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1.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205279

RESUMO

Lipoprotein subclasses possess crucial cardiometabolic information. Due to strong multicollinearity among variables, little is known about the strength of influence of physical activity (PA) and adiposity upon this cardiometabolic pattern. Using a novel approach to adjust for covariates, we aimed at determining the "net" patterns and strength for PA and adiposity to the lipoprotein profile. Principal component and multivariate pattern analysis were used for the analysis of 841 prepubertal children characterized by 26 lipoprotein features determined by proton nuclear magnetic resonance spectroscopy, a high-resolution PA descriptor derived from accelerometry, and three adiposity measures: body mass index, waist circumference to height, and skinfold thickness. Our approach focuses on revealing and validating the underlying predictive association patterns in the metabolic, anthropologic, and PA data to acknowledge the inherent multicollinear nature of such data. PA associates to a favorable cardiometabolic pattern of increased high-density lipoproteins (HDL), very large and large HDL particles, and large size of HDL particles, and decreasedtriglyceride, chylomicrons, very low-density lipoproteins (VLDL), and their subclasses, and to low size of VLDL particles. Although weakened in strength, this pattern resists adjustment for adiposity. Adiposity is inversely associated to this pattern and exhibits unfavorable associations to low-density lipoprotein (LDL) features, including atherogenic small and very small LDL particles. The observed associations are still strong after adjustment for PA. Thus, lipoproteins explain 26.0% in adiposity after adjustment for PA compared to 2.3% in PA after adjustment for adiposity.


Assuntos
Adiposidade , Fatores de Risco Cardiometabólico , Exercício Físico , Lipoproteínas/sangue , Índice de Massa Corporal , Criança , Feminino , Humanos , Lipoproteínas LDL/sangue , Masculino , Noruega , Tamanho da Partícula , Pregas Cutâneas
2.
Nutrients ; 13(4)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917778

RESUMO

The primary objective of this study was to compare weight changes in two groups of ageing Irish adults with overweight and adiposity-based chronic disease: participants who had dietary energy requirements prescribed on the base of measured RMR and participants whose RMR was estimated by a prediction equation. Fifty-four Caucasian adults (male n = 25; female n = 29, age 57.5 ± 6.3 years, weight 90.3 ± 15.1 kg, height 171.5 ± 9.5 cm, BMI 30.7 ± 4.6 kg/m2) were randomly assigned to a dietary intervention with energy prescription based on either measured RMR or estimated RMR. RMR was measured by indirect calorimetry after an overnight fast and predicted values were determined by the Mifflin et al. (1990) prediction equation. All participants received individual nutritional counselling, motivational interviewing and educational material. Anthropometric variables, blood pressure, blood glucose and blood lipid profile were assessed over 12 weeks. Body weight at week 12 was significantly lower (p < 0.05) for both groups following dietary interventions, mRMR: -4.2%; eRMR: -3.2% of initial body weight. There was no significant difference in weight loss between groups. Overall, 20.8% mRMR and 17.4% of eRMR participants experienced clinically meaningful (i.e., ≥5% of initial weight) weight reduction. Weight reduction in adults aged ≥50 years over the short term (12 weeks) favoured a reduction in blood pressure, triglycerides and glucose, thus reducing cardiovascular disease risk factors. This research indicates that employing a reduced-calorie diet using indirect calorimetry to determine energy needs when improving weight outcomes in adults (>50 years) with overweight and adiposity-based chronic disease is equal to employing a reduced-calorie diet based on the Mifflin et al. (1990) prediction equation. A reduced-energy diet based on mRMR or eRMR facilitates clinically meaningful weight reduction in adults (≥50 years) over the short term (12 weeks) and favours a reduction in blood pressure, triglycerides and glucose, thus reducing cardiovascular disease risk factors. Moreover, the addition of motivational interviewing and behaviour change techniques that support and encourage small behaviour changes is effective in short-term weight management.


Assuntos
Adiposidade , Envelhecimento/fisiologia , Metabolismo Basal/fisiologia , Dieta , Sobrepeso/dietoterapia , Descanso/fisiologia , Idoso , Glicemia/metabolismo , Colesterol/sangue , Doença Crônica , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Resultado do Tratamento , Triglicerídeos/sangue
3.
Biochem Biophys Res Commun ; 556: 192-198, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33845309

RESUMO

Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. In recent years, several studies have demonstrated that infection with H. pylori, especially strains harboring the virulence factor CagA (cytotoxin-associated gene A), contribute to the development of non-gastric systemic diseases, including hypercholesterolemia and atherosclerotic cardiovascular diseases. However, mechanisms underlying this association has not been defined. In this study, we carried out a large-scale genetic screen using Drosophila and identified a novel CagA target low-density lipoprotein receptor (LDLR), which aids in the clearance of circulating LDL. We showed that CagA physically interacted with LDLR via its carboxy-terminal region and inhibited LDLR-mediated LDL uptake into cells. Since deficiency of LDLR-mediated LDL uptake has been known to increase plasma LDL and accelerate atherosclerosis, our findings may provide a novel mechanism for the association between infection with CagA-positive H. pylori and hypercholesterolemia leading to atherosclerotic cardiovascular diseases.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidade , Lipoproteínas LDL/metabolismo , Receptores de LDL/metabolismo , Fatores de Virulência/metabolismo , Animais , Animais Geneticamente Modificados , Aterosclerose/microbiologia , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Olho/metabolismo , Feminino , Humanos , Hipercolesterolemia/microbiologia , Lipoproteínas LDL/sangue , Masculino , Ligação Proteica
4.
Nat Commun ; 12(1): 1889, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767172

RESUMO

Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the proteinase responsible for LDLR cleavage is unknown. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) co-immunoprecipitates and co-localizes with LDLR and promotes LDLR cleavage. Plasma sLDLR and cholesterol levels are reduced while hepatic LDLR is increased in mice lacking hepatic MT1-MMP. Opposite effects are observed when MT1-MMP is overexpressed. MT1-MMP overexpression significantly increases atherosclerotic lesions, while MT1-MMP knockdown significantly reduces cholesteryl ester accumulation in the aortas of apolipoprotein E (apoE) knockout mice. Furthermore, sLDLR is associated with apoB and apoE-containing lipoproteins in mouse and human plasma. Plasma levels of sLDLR are significantly increased in subjects with high plasma LDL cholesterol levels. Thus, we demonstrate that MT1-MMP promotes ectodomain shedding of hepatic LDLR, thereby regulating plasma cholesterol levels and the development of atherosclerosis.


Assuntos
Apolipoproteína B-100/sangue , Apolipoproteínas E/sangue , Aterosclerose/patologia , Lipoproteínas LDL/sangue , Metaloproteinase 14 da Matriz/metabolismo , Receptores de LDL/metabolismo , Animais , Apolipoproteínas E/genética , Linhagem Celular Tumoral , Ésteres do Colesterol/metabolismo , Dependovirus/genética , Feminino , Células HEK293 , Células Hep G2 , Humanos , Masculino , Metaloproteinase 14 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
5.
BMC Infect Dis ; 21(1): 294, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757439

RESUMO

BACKGROUND: HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. METHODS: This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n = 5) and HIV negative patients (controls: n = 5) were analysed for miR-148a and mRNA expression using quantitative PCR. RESULTS: Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/L; p = 0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. CONCLUSIONS: Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.


Assuntos
Colelitíase/metabolismo , Colesterol/metabolismo , Infecções por HIV/metabolismo , Metabolismo dos Lipídeos/genética , Lipoproteínas LDL/sangue , Fígado/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Adulto , Fármacos Anti-HIV/uso terapêutico , Colelitíase/tratamento farmacológico , Colelitíase/etiologia , Colelitíase/genética , Feminino , Regulação da Expressão Gênica , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Receptores de LDL/genética , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
7.
Nutrients ; 13(2)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33669954

RESUMO

The therapeutic effects of curcumin for polycystic ovary syndrome (PCOS) remain inconclusive. The present study aims to evaluate the effects of curcumin on glycemic control and lipid profile in patients with PCOS. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from the inception through 28 November 2020. Randomized control trials (RCTs), which enrolled adult patients with PCOS, compared curcumin with placebo regarding the glycemic control and lipid profile, and reported sufficient information for performing meta-analysis, were included. Three RCTs were included. Curcumin significantly improves fasting glucose (mean difference (MD): -2.77, 95% confidence interval (CI): -4.16 to -1.38), fasting insulin (MD: -1.33, 95% CI: -2.18 to -0.49), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (MD: -0.32, 95% CI: -0.52 to -0.12), and quantitative insulin sensitivity check index (QUICKI) (MD: 0.010, 95% CI: 0.003-0.018). It also significantly improves high-density lipoprotein (MD: 1.92, 95% CI: 0.33-3.51) and total cholesterol (MD: -12.45, 95% CI: -22.05 to -2.85). In contrast, there is no statistically significant difference in the improvement in low-density lipoprotein (MD: -6.02, 95% CI: -26.66 to 14.62) and triglyceride (MD: 8.22, 95% CI: -26.10 to 42.53) between curcumin and placebo. The results of the fasting glucose, fasting insulin, HOMA-IR, QUICKI, and total cholesterol are conclusive as indicated by the trial sequential analysis. Curcumin may improve glycemic control and lipid metabolism in patients with PCOS and metabolic abnormality without significant adverse effects. Further studies are advocated to investigate the potential effects of curcumin on hyperandrogenism.


Assuntos
Curcumina/farmacologia , Controle Glicêmico , Lipídeos/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/terapia , Adulto , Glicemia/efeitos dos fármacos , Colesterol/sangue , Suplementos Nutricionais , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
8.
Nutrients ; 13(2)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670720

RESUMO

Alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), rumenic acid (RmA), and punicic acid (PunA) are claimed to influence several physiological functions including insulin sensitivity, lipid metabolism and inflammatory processes. In this double-blind randomized controlled trial, we investigated the combined effect of ALA, DHA, RmA and PunA on subjects at risk of developing metabolic syndrome. Twenty-four women and men were randomly assigned to two groups. Each day, they consumed two eggs enriched with oleic acid (control group) or enriched with ALA, DHA, RmA, and PunA (test group) for 3 months. The waist circumference decreased significantly (-3.17 cm; p < 0.001) in the test group. There were no major changes in plasma insulin and blood glucose in the two groups. The dietary treatments had no significant effect on endothelial function as measured by peripheral arterial tonometry, although erythrocyte nitrosylated hemoglobin concentrations tended to decrease. The high consumption of eggs induced significant elevations in plasma low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (p < 0.001), which did not result in any change in the LDL/HDL ratio in both groups. These results indicate that consumption of eggs enriched with ALA, DHA, RmA and PunA resulted in favorable changes in abdominal obesity without affecting other factors of the metabolic syndrome.


Assuntos
Dieta/métodos , Ovos , Ácidos Graxos Insaturados/administração & dosagem , Alimentos Fortificados , Síndrome Metabólica/prevenção & controle , Obesidade Abdominal/dietoterapia , Adulto , Idoso , Fatores de Risco Cardiometabólico , HDL-Colesterol/sangue , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Ácidos Linoleicos Conjugados/administração & dosagem , Ácidos Linolênicos/administração & dosagem , Lipoproteínas LDL/sangue , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/complicações , Circunferência da Cintura , Ácido alfa-Linoleico/administração & dosagem
9.
J Sports Sci Med ; 20(1): 133-141, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33707996

RESUMO

Strength training can improve myriad health parameters in elderly cohorts. Although potentially more appropriate for the elderly, low-load resistance training protocols have been less investigated. We aimed to examine the effects of 12 weeks of chair-based, low-load resistance training with elastic band (EBT) on functional fitness and metabolic biomarkers in older women. One hundred sixty-eight women were allocated randomly to an elastic band resistance training (EBT, n = 86, 75.7 ± 8.9 years, 71.3 ± 12.2 kg) or a control group (CON, n = 82, 74.5 ± 8.2years, 70.6 ± 12.0 kg). RT protocol consisted of periodized chair-based, low-load whole-body resistance exercises (2 sets, 12-15 repetitions, 40-60% of one repetition maximum-1RM) using an elastic band, twice weekly for 12 weeks. The resistance training program was generally designed to maintain internal load over time, provided with increasing intensity using various elastic bands (Thera-Band). Functional fitness (30-s Chair Stand,30-s Arm Curl, 2-min Step Test, Chair Sit-and-Reach, Back Scratch, 8-Foot Up-and-Go, Handgrip Strength) and metabolic markers (Fasting blood glucose, triglycerides, total cholesterol, high (HDL) and low (LDL) density lipoprotein) were measured before and after the training period. To detect pre/post intervention changes and between group- differences 2x2 repeated measures ANOVA was applied. Significant improvements over time for all fitness variables for EBT comparing to CON were obtained (F = 12.78, p < 0.05 for 30-s Chair Stand; F = 14.04, p < 0.05 for 30-s Arm Curl; F = 5.18, p < 0.05 for 2-min Step Test; F = 10.90, p < 0.05 for Chair Sit-and-Reach; F = 16.57, p < 0.05 for Back Scratch; F = 11.79, p < 0.05 for 8-foot Up-and-Go; and F = 29.25, p < 0.05 for Handgrip Strength). In addition, significant improvements over time for all but one (triglycerides) biomarkers for EBT comparing to CON were obtained (F = 7.30, p < 0.05 for blood sugar levels; F = 13.36, p < 0.05 for total cholesterol; F = 8.61, p < 0.05 for HDL; and F = 11.53, p < 0.05 for LDL). Furthermore, the participants' adherence to training sessions of over 90% was reported. In conclusion, 12 weeks of EBT is safe and beneficial for improving health-related fitness and metabolic biomarkers in older women and seems to be viable model to ensure a high training adherence rate.


Assuntos
Biomarcadores/sangue , Aptidão Física/fisiologia , Desempenho Físico Funcional , Treinamento de Força/métodos , Postura Sentada , Idoso , Análise de Variância , Glicemia/análise , Colesterol/sangue , Jejum/sangue , Feminino , Força da Mão/fisiologia , Humanos , Lipoproteínas LDL/sangue , Treinamento de Força/instrumentação , Sérvia , Método Simples-Cego , Triglicerídeos/sangue
10.
Biochem Biophys Res Commun ; 552: 37-43, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33740663

RESUMO

Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.


Assuntos
Apoptose/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Grelina/farmacologia , Inflamação/prevenção & controle , MAP Quinase Quinase 4/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Aterosclerose/prevenção & controle , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Grelina/administração & dosagem , Inflamação/metabolismo , Inflamação/fisiopatologia , Injeções Intraperitoneais , Lipoproteínas LDL/antagonistas & inibidores , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Masculino , Camundongos Knockout , Pericitos/citologia , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Medicine (Baltimore) ; 100(7): e24722, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607814

RESUMO

ABSTRACT: Excessive iron accumulation provokes toxic effects, especially in the cardiovascular system. Under iron overload, labile free non-transferrin-bound iron (NTBI) can induce cardiovascular damage with increased oxidative stress. However, the significance of NTBI in individuals without iron overload and overt cardiovascular disease has not been investigated. We aimed to examine the distribution of serum NTBI and its relationship with oxidative stress and cardiac load under physiological conditions in the general population.We enrolled individuals undergoing an annual health check-up and measured serum NTBI and derivatives of reactive oxygen metabolites (d-ROM), an oxidative stress marker. In addition, we evaluated serum levels of B-type natriuretic peptide (BNP) to examine cardiac load. We excluded patients with anemia, renal dysfunction, cancer, active inflammatory disease, or a history of cardiovascular disease.A total of 1244 individuals (57.8 ±â€Š11.8 years) were enrolled, all of whom had detectable serum NTBI. d-ROM and BNP showed significant trends across NTBI quartiles. Multivariable regression analysis revealed that serum iron and low-density lipoprotein cholesterol were positively associated with NTBI but that age, d-ROM, and BNP showed an inverse association with this measure. In logistic regression analysis, NTBI was independently associated with a combination of higher levels of both d-ROM and BNP than the upper quartiles after adjustment for possible confounding factors.Serum NTBI concentration is detectable in the general population and shows significant inverse associations with oxidative stress and cardiac load. These findings indicate that serum NTBI in physiological conditions does not necessarily reflect increased oxidative stress, in contrast to the implications of higher levels in states of iron overload or pathological conditions.


Assuntos
Débito Cardíaco/fisiologia , Sistema Cardiovascular/metabolismo , Sobrecarga de Ferro/complicações , Ferro/sangue , Estresse Oxidativo/fisiologia , Idoso , Sistema Cardiovascular/fisiopatologia , Estudos Transversais , Feminino , Ferritinas/sangue , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Transferrina/análise
12.
Nutrients ; 13(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572735

RESUMO

Dietary fatty acids (FA) are essential for overall human health, yet individual FA reference ranges have yet to be established. Developing individual FA reference ranges can provide context to reported concentrations and whether an individual displays deficient, or excess amounts of FA. Reference ranges of sixty-seven individual FA (µmol/L) were profiled and analyzed using gas chromatography with a flame ionization detector from serum samples collected from 476 middle-aged Singaporean males (BMI:23.3 ± 2.9) and females (BMI:21.8 ± 3.6). Measures of triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) (mmol/L) were also collected. The mean FA concentration seen in this cohort (11,458 ± 2478 was similar to that of overweight North American cohorts assessed in past studies. Ten biologically relevant FA were compared between sexes, with females exhibiting significantly higher concentrations in four FA (p < 0.05). A multiple regression model revealed the ten FA contributed significantly to nearly all lipid biomarkers (p < 0.05). A majority of participants who had FA concentrations in the ≥95th percentile also exhibited TG, HDL, LDL, and TC levels in the "high" risk classification of developing cardiovascular disease. Future studies profiling individual FA reference ranges in many unique, global cohorts are necessary to develop cut-off values of individual FA concentrations highly related to disease-risk.


Assuntos
Doenças Cardiovasculares/etiologia , Colesterol/sangue , Ácidos Graxos/sangue , Lipoproteínas/sangue , Triglicerídeos/sangue , Antropometria , Biomarcadores/sangue , Índice de Massa Corporal , Cromatografia Gasosa , Feminino , Voluntários Saudáveis , Fatores de Risco de Doenças Cardíacas , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Medição de Risco , Singapura
13.
ACS Appl Mater Interfaces ; 13(3): 4583-4592, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33448218

RESUMO

A salt-responsive nanoplatform is constructed through a simple tactic by tethering zwitterionic nanohydrogels (NGs) on a carboxylated silica (SiO2-COOH) framework. Chondroitin sulfate (CS), with a specific recognition effect for low-density lipoprotein (LDL), is modified to NGs by amidation reaction. Water retention and swelling properties of NGs are greatly enhanced in a saline environment attributed to the anti-polyelectrolyte effect. It endows the SiO2-NGs-CS framework a sensitive salt-responsive property, and thus, more CS moieties are exposed. The controlled adsorption of LDL with an adsorption efficiency of 7.2 to 93% is achieved by adjusting the concentration of MgCl2 from 0 to 0.1 mol L-1. SiO2-NGs-CS exhibits excellent adsorption capacity for fishing LDL, acquiring the highest adsorption capacity of 898.1 mg g-1. Moreover, SiO2-NGs-CS shows superior selectivity to the other three proteins with similar isoelectric points (pIs) to LDL. The captured LDL is readily stripped by 0.2% (m/m) SDS with a recovery of 95.4%. The superior separation performance of SiO2-NGs-CS is demonstrated by the isolation and selective discrimination of LDL from the simulated serum of hypercholesterolemia patients, as illustrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis assays.


Assuntos
Sulfatos de Condroitina/química , Hidrogéis/química , Lipoproteínas LDL/isolamento & purificação , Nanogéis/química , Dióxido de Silício/química , Adsorção , Animais , Bovinos , Eletroforese em Gel de Poliacrilamida , Humanos , Lipoproteínas LDL/sangue , Cloreto de Magnésio/química
14.
Phytomedicine ; 83: 153467, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516143

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) KaiXinSan (KXS) has been used to treat depressed patients for a long time, but its potential underlying mechanisms have not been fully understood. HYPOTHESIS: KXS could mitigate symptoms of patients with atypical depression at least partly via regulating lipid equilibrium. METHODS: Patients meeting DSM-IV criteria for mild or moderate depression were assigned into placebo (N = 68) or KXS 3.2 g/day (N = 66) groups in a randomized, double-blinded, placebo-controlled, parallel clinical trial to investigate the anti-depressive efficacy of KXS and its association with serum lipid profile. RESULTS: The HAMD score and SDS score at 8 weeks were significantly improved in KXS-treated patients the N-BACK accuracy rate was also increased after 8 weeks of KXS treatment compared with baseline. These results indicated that KXS not only improved the specific symptoms of depression, but also had a beneficial effect on cognitive function related working memory. More importantly, KXS treatment improved patients' lipid profile by reducing the ratios of LDL/HDL and ApoB/ApoA1 (p < 0.05), as well as ApoC3 level. Moreover, subgroup analysis found that HAMD score was significantly higher in patients with high lipid profile than in those with normal lipid profile, and lipid improvement after 8 weeks of KXS treatment was more obvious in depressed patients with high lipid profile than with normal lipid profile. CONCLUSION: KXS could mitigate symptoms of patients with minor and modest depression at least partly via regulating lipid equilibrium. Its might shed light that KXS may likely contributes to depressed patients with other cardio-metabolic diseases.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Lipídeos/sangue , Adulto , Antidepressivos/uso terapêutico , Apolipoproteína C-III/sangue , Apolipoproteínas B/sangue , Depressão/metabolismo , Depressão/psicologia , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
15.
Medicine (Baltimore) ; 100(2): e24269, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466214

RESUMO

ABSTRACT: Cystatin C has been proposed as a useful biomarker of early impaired kidney function and a predictor of mortality risk. The present study is to investigate the association between serum Cystatin C and the severity of coronary artery lesions, Gensini score (GS), and the risk of coronary artery disease (CAD).A total of 682 CAD patients (230 females, 452 males; mean age 62.6 ±â€Š10.7 years, range from 31 to 86 years) and 135 controls (41 females, 94 males; mean age 58.0 ±â€Š10.3 years, range from 38 to 84 years) were recruited in the present study. Enzyme-linked immunosorbent assay was applied to measure serum cystatin C levels and other serum indexes. The estimated glomerular filtration rate and GS were calculated.Serum low-density lipoprotein cholesterol (LDL-C), uric acid, Cystatin C, and homocysteine (HCY) were significantly elevated in CAD patients compared to controls. There were significant differences regarding total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, cystatin C, eGFR and GS among stable angina pectoris (SAP), unstable angina group (UAP), and acute myocardial infarction (AMI) patients. AMI group had an elevated serum Cystatin C, LDL-C, HCY, and GS than SAP and UAP patients. When stratified patient groups by the quartiles of Cystatin C, we found age, the proportion of male and patients with diabetes, HCY, and GS were increased in Q4 than in other quartile groups. Spearman correlation test revealed a positive relationship between Cystatin C, HCY, and GS. Multivariate logistic regression analysis revealed that serum Cystatin C level, presence of hypertension and diabetes, HCY, age, and male were the risk factors for coronary artery lesions.In summary, our results suggested that cystatin C is a promising clinical biomarker that provides complementary information to the established risk determinants. The serum Cystatin C level is strongly associated with GS and could be used to evaluate the severity of coronary artery lesions.


Assuntos
Doença da Artéria Coronariana/etiologia , Cistatina C/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Colesterol/sangue , Feminino , Taxa de Filtração Glomerular , Fatores de Risco de Doenças Cardíacas , Homocisteína/sangue , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Triglicerídeos/sangue , Ácido Úrico/sangue
16.
Arterioscler Thromb Vasc Biol ; 41(3): 1229-1238, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33504178

RESUMO

OBJECTIVE: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD. CONCLUSIONS: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Lipídeos/sangue , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Humanos , Lipoproteínas/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Doença Arterial Periférica/etiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue
17.
Rheumatology (Oxford) ; 60(2): 866-871, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32844232

RESUMO

OBJECTIVES: SLE patients have an enhanced risk of atherosclerosis and cardiovascular disease. However, the increased prevalence of cardiovascular disease is not fully explained by traditional Framingham cardiovascular risk factors. Specific features of low-density lipoprotein (LDL) particles, other than plasma concentration, may induce accelerated atherosclerosis at early stages in these patients. Thus, we aimed to explore the impact of LDL from both active and inactive SLE patients on human aortic endothelial cells. METHODS: Human aortic endothelial cells were stimulated with the same concentration of LDL particles isolated from pooled serum that was collected from 13 SLE patients during both active and inactive states. Gene expression and cell migration assays were performed. RESULTS: Circulating LDL particles obtained from healthy volunteers and SLE patients in both remission and flare states were comparable in terms of number, cholesterol and triglyceride content, and net electric charge. Stimulation of cells with LDL from active SLE patients induced the expression of vascular cell adhesion molecule 1 (∼2.0-fold, P < 0.05), monocyte chemoattractant protein 1 (∼2.0-fold, P < 0.05) and matrix metallopeptidase 2 (∼1.6-fold, P < 0.01) compared with cells stimulated with LDL from inactive SLE patients. Additionally, LDL extracted from active patients increased cell migration in a wound-healing assay (1.4-fold, P < 0.05). CONCLUSION: Our data show that, at the same LDL concentration, LDL from active SLE patients had increased proatherogenic effects on endothelial cells compared with LDL from the same patients when in an inactive or remission state.


Assuntos
Aterosclerose/metabolismo , Quimiocina CCL2/metabolismo , Lipoproteínas LDL , Lúpus Eritematoso Sistêmico , Metaloproteinase 2 da Matriz/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Aorta/patologia , Ensaios de Migração Celular/métodos , Células Cultivadas , Correlação de Dados , Progressão da Doença , Células Endoteliais/metabolismo , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/metabolismo , Gravidade do Paciente
18.
J Stroke Cerebrovasc Dis ; 30(2): 105417, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33307290

RESUMO

OBJECTIVE: To investigate whether utilizing a LDL-direct laboratory test rather than a lipid panel to determine LDL-C as part of the inpatient stroke and TIA workup is more cost-effective to the patient and hospital system. A retrospective analysis was conducted on all patients admitted to UCSD La Jolla and Hillcrest Hospital and discharged with a final diagnosis of ischemic stroke or transient ischemic attack between 7/2016 and 6/2019. A cost-analysis was extrapolated based on the current cost of each test as provided by the UCSD hospital billing department as of June 2020. Patients started on a statin, who were not on one prior to admission, were also analyzed to highlight the importance of an accurate LDL-C on management of dyslipidemia. RESULTS: A total of 1245 patients were included in the study with 87% representing Ischemic strokes and 13% transient ischemic attacks. Over the three-year period, a total savings of $77,545 would be achieved if LDL-direct were used in place of a lipid-panel, representing an overall cost savings of 33%. Over the same time-frame, 536 (43%) patients were started on a statin that were not previously on one. CONCLUSIONS: Ordering a LDL-direct test should be considered over a lipid panel to evaluate LDL-C as it may prove to be the most cost effective approach to both the patient and Healthcare system.


Assuntos
Análise Química do Sangue/economia , Dislipidemias/diagnóstico , Dislipidemias/economia , Custos Hospitalares , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/economia , AVC Isquêmico/diagnóstico , Lipoproteínas LDL/sangue , Biomarcadores/sangue , California , Redução de Custos , Análise Custo-Benefício , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pacientes Internados , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/tratamento farmacológico , AVC Isquêmico/sangue , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/economia , Valor Preditivo dos Testes , Estudos Retrospectivos
19.
Nature ; 589(7841): 287-292, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33268892

RESUMO

Cardiovascular disease (CVD) is the leading cause of mortality in the world, with most CVD-related deaths resulting from myocardial infarction or stroke. The main underlying cause of thrombosis and cardiovascular events is atherosclerosis, an inflammatory disease that can remain asymptomatic for long periods. There is an urgent need for therapeutic and diagnostic options in this area. Atherosclerotic plaques contain autoantibodies1,2, and there is a connection between atherosclerosis and autoimmunity3. However, the immunogenic trigger and the effects of the autoantibody response during atherosclerosis are not well understood3-5. Here we performed high-throughput single-cell analysis of the atherosclerosis-associated antibody repertoire. Antibody gene sequencing of more than 1,700 B cells from atherogenic Ldlr-/- and control mice identified 56 antibodies expressed by in-vivo-expanded clones of B lymphocytes in the context of atherosclerosis. One-third of the expanded antibodies were reactive against atherosclerotic plaques, indicating that various antigens in the lesion can trigger antibody responses. Deep proteomics analysis identified ALDH4A1, a mitochondrial dehydrogenase involved in proline metabolism, as a target antigen of one of these autoantibodies, A12. ALDH4A1 distribution is altered during atherosclerosis, and circulating ALDH4A1 is increased in mice and humans with atherosclerosis, supporting the potential use of ALDH4A1 as a disease biomarker. Infusion of A12 antibodies into Ldlr-/- mice delayed plaque formation and reduced circulating free cholesterol and LDL, suggesting that anti-ALDH4A1 antibodies can protect against atherosclerosis progression and might have therapeutic potential in CVD.


Assuntos
1-Pirrolina-5-Carboxilato Desidrogenase/imunologia , Aterosclerose/imunologia , Aterosclerose/prevenção & controle , Autoanticorpos/imunologia , Autoantígenos/imunologia , 1-Pirrolina-5-Carboxilato Desidrogenase/sangue , Animais , Aterosclerose/sangue , Aterosclerose/diagnóstico , Autoanticorpos/sangue , Autoanticorpos/genética , Autoantígenos/sangue , Autoimunidade , Linfócitos B/imunologia , Biomarcadores/sangue , Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Progressão da Doença , Humanos , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/prevenção & controle , Proteômica , Receptores de LDL/deficiência , Receptores de LDL/genética , Análise de Célula Única
20.
Clin Immunol ; 222: 108637, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232825

RESUMO

Cardiometabolic status is a key factor in mortality by cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). This study evaluated the association of cardiometabolic risk status with clinical activity and damage in SLE patients. A cross-sectional study was conducted in 158 SLE patients and 123 healthy subjects (HS). Anthropometry, glucose, hs-CRP, lipid profile, oxLDL, sCD36, anti-oxLDL antibodies, and cardiometabolic indexes were evaluated. SLE patients had dyslipidemia, higher sCD36, anti-oxLDL antibodies, hs-CRP, and risk (OR > 2) to present Castelli score ≥ 4.5, HDL-C < 40 mg/dL and LDL-C ≥ 100 mg/dL. Disease evolution time was correlated with glucose and BMI, damage with TG, and clinical activity with TG, TG/HDL-C ratio, and Kannel index. Active SLE patients had risk (OR > 2) to present a Castelli score ≥ 4.5, Kannel score ≥ 3, TG/HDL-C ratio ≥ 3 and HDL-C < 40 mg/dL. In conclusion, SLE patients have high cardiometabolic risk to CVD related to disease evolution time, and clinical activity.


Assuntos
Doenças Cardiovasculares/epidemiologia , Dislipidemias/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Adulto , Glicemia/análise , Índice de Massa Corporal , Proteína C-Reativa/análise , Antígenos CD36/sangue , Colesterol/sangue , Estudos Transversais , Dislipidemias/patologia , Feminino , Glucose/metabolismo , Humanos , Lipoproteínas LDL/sangue , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco
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