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1.
J Agric Food Chem ; 67(48): 13307-13317, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679333

RESUMO

Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.


Assuntos
Anticolesterolemiantes/metabolismo , Hipercolesterolemia/dietoterapia , Polissacarídeos Bacterianos/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
2.
World Neurosurg ; 132: e99-e108, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518751

RESUMO

BACKGROUND: High cholesterol has been correlated with a greater risk of cerebrovascular diseases. Whether pre-existing high cholesterol exacerbates traumatic brain injury (TBI), and whether treatment with the cholesterol-lowering agent simvastatin has neuroprotective effects, especially anti-neuroinflammatory effects, after TBI are not well investigated. METHODS: Five-week-old male Sprague-Dawley rats were fed a high-fat diet for 8 weeks to induce hypercholesterolemia. Anesthetized male Sprague-Dawley rats were divided into 5 groups, including the sham-operated control, TBI control, and TBI with simvastatin treatment (4 mg/kg, 10 mg/kg, or 20 mg/kg) groups. Simvastatin was intraperitoneally injected at 0, 24, and 48 hours after TBI. Motor function was measured using an inclined plane. Neuronal apoptosis (maker Neu-N, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling), tumor necrosis factor-α expression in microglia (marker OX42) and astrocytes (marker glial fibrillary acidic protein), and Tumor necrosis factor-alpha receptor (TNFR) 1 and TNFR2 expression in neurons in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the third day after TBI. RESULTS: TBI significantly increased the serum levels of cholesterol. The TBI-induced motor deficit was significantly attenuated by 4, 10, and 20 mg/kg simvastatin therapy on the third day after TBI. TBI-induced neuronal TNFR1 activation and apoptosis, as well as tumor necrosis factor-α expression in astrocytes in the ischemic cortex, were significantly attenuated by simvastatin, particularly when 20 mg/kg was administered. Simultaneously, the serum cholesterol remained high despite simvastatin treatment. CONCLUSIONS: The neuroprotection effects of simvastatin on the pre-existing hypercholesterolemia during TBI in rats may be related to its anti-neuroinflammatory effects but not to its cholesterol-lowing effects.


Assuntos
Anticolesterolemiantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , Fármacos Neuroprotetores/uso terapêutico , Sinvastatina/uso terapêutico , Animais , Lesões Encefálicas Traumáticas/psicologia , Colesterol/sangue , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/biossíntese , Fator de Necrose Tumoral alfa/sangue
3.
J Exp Clin Cancer Res ; 38(1): 404, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519191

RESUMO

BACKGROUND: Metabolic reprogramming is an important characteristic of tumors. In the progression of pituitary adenomas (PA), abnormal glucose metabolism has been confirmed by us before. However, whether cholesterol metabolism is involved in the process of PA remains unclear. This study aimed to investigate whether abnormal cholesterol metabolism could affect the progression of PA. METHODS: We analyzed the expression of sterol carrier protein 2 (SCP2) in 40 surgical PA samples. In vitro experiments and xenograft models were used to assess the effects of SCP2 and cholesterol on proliferation of PA. The incidence of hypercholesterolemia between 140 PA patients and 100 heathy controls were compared. RESULTS: We found an upregulation of SCP2 in PA samples, especially in tumors with high proliferation index. Forced expression of SCP2 promoted PA cell lines proliferation in vitro. Furthermore, SCP2 regulated cholesterol trafficking from cytoplasm to membrane in GH3 cells, and extracellularly treating GH3 cells and primary PA cells with methyl-ß-cyclodextrin/cholesterol complex to mimic membrane cholesterol concentration enhanced cell proliferation, which suggested a proliferative effect of cholesterol. Mechanistically, cholesterol induced activation of PKA/SUFU/GLI1 signaling via smoothened receptor, which was well-known as Hedgehog signaling, resulting in inhibiting apoptosis and promoting cell cycle. Accordingly, activation of Hedgehog signaling was also confirmed in primary PA cells and surgical PA samples. In vivo, SCP2 overexpression and high cholesterol diet could promote tumor growth. Intriguingly, the incidence of hypercholesterolemia was significantly higher in PA patients than healthy controls. CONCLUSIONS: Our data indicated that dysregulated cholesterol metabolism could promote PA growth by activating Hedgehog signaling, supporting a potential tumorigenic role of cholesterol metabolism in PA progression.


Assuntos
Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Proteínas Hedgehog/metabolismo , Neoplasias Hipofisárias/metabolismo , Transdução de Sinais , Adulto , Idoso , Animais , Transporte Biológico , Biomarcadores , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Feminino , Xenoenxertos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Hipofisárias/etiologia , Neoplasias Hipofisárias/patologia , Ratos
4.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
5.
Lipids Health Dis ; 18(1): 148, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272450

RESUMO

BACKGROUND: The present research project was designed to evaluate the cholesterol lowering potential of different date varieties including one exotic (Ajwa) and three Pakistani varieties (Aseel, Khudravi, Hallawi). METHODS: The albino rats were divided into six groups on the basis of different diets which includes, control having basal diet, high cholesterol high sucrose diet, high cholesterol high sucrose diet plus Khudravi dates, high cholesterol high sucrose diet plus Hallawi dates, high cholesterol high sucrose diet plus Aseel dates, high cholesterol high sucrose diet plus Ajwa dates to evaluate maximum cholesterol lowering potential of each date variety. RESULTS: The results showed that Hallawi and Ajwa have lower crude fiber content as 2.02 ± 0.03% and 2.43 ± 0.04% however, lowest crude fat content (0.26 ± 0.01%) was also observed in ajwa. Mineral profile depicted that sodium (9.50-18.00 mg/100 g) was found to be in lesser amount among all varieties whereas, higher amount of potassium (465.00 to 887.20 mg/100 g) depicted that it is suitable for people having hypertension. Higher amount of reducing sugar was also observed in ajwa (79.45 ± 1.22%) followed by Hallawi (77.68 ± 1.42%). Total phenolic contents were found higher in Aseel (291.36 mg/100 g) whereas, minimum was observed in Khudravi (232.64 mg/100 g). Furthermore, date varieties were also examined rat modeling to evaluate their maximum cholesterol lowering efficiency. Ajwa and Hallawi were observed to suppress the cholesterol efficiently as 110 mg/dL and 103 mg/dL respectively. On the basis of chemical profiling and other parameters, two date varieties Ajwa and Hallawi showed almost similar results and found to have maximum serum cholesterol, LDL and triglyceride reduction potential with good kidney and liver functions. Functional date bar was also developed by using Hallawi variety andsubjected to sensory evaluation. CONCLUSION: In nutshell, Hallawi date variety was considered as better cholesterol lowering potential among other indigenous varieties and very close to Ajwa variety. So that Hallawi can be used to suppress the deadly effects of obesity and allied discrepancies particularly hypercholesterolemia.


Assuntos
Alimento Funcional , Hipercolesterolemia/prevenção & controle , Phoeniceae/química , Animais , Antioxidantes/análise , Colesterol/sangue , Modelos Animais de Doenças , Alimento Funcional/análise , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Minerais/análise , Valor Nutritivo , Paquistão , Fenóis/análise , Ratos Sprague-Dawley , Paladar , Triglicerídeos/sangue
6.
Artigo em Inglês | MEDLINE | ID: mdl-31349672

RESUMO

Lead, mercury, and cadmium are common environmental pollutants in industrialized countries, but their combined impact on hypercholesterolemia (HC) is poorly understood. The aim of this study was to compare the performance of various machine learning (ML) models to predict the prevalence of HC associated with exposure to lead, mercury, and cadmium. A total of 10,089 participants of the Korea National Health and Nutrition Examination Surveys 2008-2013 were selected and their demographic characteristics, blood concentration of metals, and total cholesterol levels were collected for analysis. For prediction, five ML models, including logistic regression (LR), k-nearest neighbors, decision trees, random forests, and support vector machines (SVM) were constructed and their predictive performances were compared. Of the five ML models, the SVM model was the most accurate and the LR model had the highest area under receiver operating characteristic (ROC) curve of 0.718 (95% CI: 0.688-0.748). This study shows the potential of various ML methods to predict HC associated with exposure to metals using population-based survey data.


Assuntos
Cádmio/toxicidade , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Hipercolesterolemia/etiologia , Chumbo/toxicidade , Aprendizado de Máquina , Mercúrio/toxicidade , Adulto , Árvores de Decisões , Feminino , Previsões , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , República da Coreia/epidemiologia , Máquina de Vetores de Suporte
7.
Life Sci ; 233: 116702, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356905

RESUMO

AIMS: We previously demonstrated that iron overload induces endothelial dysfunction and oxidative stress, which could increase the risk for atherosclerosis. However, the iron-related harmfulness under a genetic predisposition to atherosclerosis is still unclear. Here, we have tested the hypothesis that chronic iron overload may change vascular reactivity associated with worsening of the atherosclerotic process in apolipoprotein E knockout (apoE(-/-)) mice. MAIN METHODS: Serum and aortas of wild-type (WT) and apoE(-/-) mice injected with iron-dextran (IO, 10 mg/mouse/day, ip) or saline 5 times a week for 4 weeks, were used. KEY FINDINGS: Iron overload increased serum levels of iron and biomarkers of liver injury and oxidative stress, and iron deposition in the aorta in both lines, but only apoE(-/-) IO mice had intensified hypercholesterolemia and atherosclerosis. By scanning electron microscopy, the small endothelial structural damage caused by iron in WT was worsened in the apoE(-/-) group. However, endothelial dysfunction was found only in the apoE(-/-) IO group, identified by impaired relaxation to acetylcholine and hyperreactivity to phenylephrine associated with reduced nitric oxide modulation. Moreover, tiron and indomethacin attenuated reactivity to phenylephrine with greater magnitude in aortas of the apoE(-/-) IO group. Confirming, there were changes in the antioxidant (superoxide dismutase and catalase) activity, increased expression of cyclooxygenase-2 in the aorta and elevated levels of thromboxane A2 and prostacyclin metabolites in the urine of apoE(-/-) IO. SIGNIFICANCE: Our results showed that chronic iron overload intensifies the atherosclerotic process and induces endothelial dysfunction in atherosclerotic mice, probably due to the oxidative stress and the imbalance between the relaxing and contractile factors synthesized by the damaged endothelium.


Assuntos
Apolipoproteínas E/fisiologia , Aterosclerose/patologia , Endotélio Vascular/patologia , Hipercolesterolemia/patologia , Sobrecarga de Ferro/complicações , Estresse Oxidativo , Acetilcolina/metabolismo , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Feminino , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Óxido Nítrico/metabolismo
8.
J Orthop Surg Res ; 14(1): 172, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182124

RESUMO

BACKGROUND: Increased tendon pain and tendon damage is a significant complication related to hyperlipidemia. Unlike the well-established pathogenesis associated with increased serum concentrations of total cholesterol, triglycerides, and low-density lipoprotein in atherosclerotic cardiovascular disease, the role of hyperlipidemia in promoting tendon damage remains controversial and requires mechanistic clarity. METHODS: In this study, we analyzed the consequences of hypercholesterolemia on the integrity of the collagen-based architecture of the Achilles tendon. The Achilles tendons from rabbits fed with normal-cholesterol (nCH) and high-cholesterol (hCH) diets were analyzed. We studied the morphology of tendons, distribution of lipids within their collagen-rich milieu, the relative amounts of fibrillar collagen I and collagen III, and selected biomechanical parameters of the tendons at the macroscale and the nanoscale. RESULTS: Histological assays of hCH tendons and tenosynovium demonstrated hypercellular areas with increased numbers of macrophages infiltrating the tendon structure as compared to the nCH tendons. While Oil Red staining revealed lipid-rich deposits in the hCH tendons, hybridization of tendon tissue with the collagen hybridizing peptide (CHP) demonstrated damage to the collagen fibers. Fourier-transform infrared (FTIR) spectra showed the presence of distinct peaks consistent with the presence of cholesterol ester. Additionally, the hCH tendons displayed regions of poor collagen content that overlapped with lipid-rich regions. The hCH tendons had a substantial fourfold increase in the collage III to collagen I ratio as compared to the nCH tendons. Tendons from the hCH rabbits showed poor biomechanical characteristics in comparison with control. The biomechanical changes were evident at the macrolevel and the nanolevel of tendon structure. CONCLUSIONS: Our findings support the hypothesis that hypercholesterolemia coincides with the weakening of the tendons. It is likely that the intimate contact between collagen fibrils and cholesterol deposits contributes to the weakening of the fibrillar structure of the tendons.


Assuntos
Tendão do Calcâneo/metabolismo , Tendão do Calcâneo/patologia , Colesterol/metabolismo , Modelos Animais de Doenças , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Animais , Colágeno/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Hipercolesterolemia/etiologia , Coelhos
9.
Niger Postgrad Med J ; 26(2): 138-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31187755

RESUMO

Glycogen storage disease (GSD) is a rare inborn error of metabolism with an incidence of 1/20,000-40,000 live births. Some of the presenting clinical features can mimic diseases commonly seen in the tropics and subtropics. We report a 14-month-old Nigerian child who presented at our institution with GSD Type 111a to alert physicians on the need to consider and recognise this rare disorder. The child presented with progressive abdominal swelling due to marked hepatomegaly. From the clinical history, the only clue to hypoglycaemia was that she eats very frequently. Her random blood sugar was normal; however, fasting blood sugar was low. The diagnosis was further entertained with laboratory results showing hypercholesterolaemia and uricaemia and confirmed by histology of biopsied liver tissue. GSD should be suspected in a child with unexplained hepatomegaly and investigated accordingly.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Doença de Depósito de Glicogênio Tipo III/diagnóstico , Hepatomegalia/etiologia , Fígado/patologia , Biópsia , Feminino , Doença de Depósito de Glicogênio Tipo III/patologia , Humanos , Hipercolesterolemia/etiologia , Hiperuricemia/etiologia , Lactente , Fígado/metabolismo , Nigéria
10.
J Pediatr Endocrinol Metab ; 32(6): 561-568, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31129653

RESUMO

Background Severe obesity is associated with a number of cardiometabolic risk factors. Thyroid-stimulating hormone (TSH) levels are often slightly increased in children with obesity. The clinical significance of the mild elevation in TSH in children with obesity is unclear. Objective To examine the association between TSH and lipids in children with severe obesity. Methods We performed a retrospective analysis of records of children with severe obesity with simultaneous measurements of TSH and lipids. Children with TSH <0.3 mIU/L and ≥10 mIU/L were excluded. The relationship between TSH and lipids was evaluated using univariate/multiple variable linear and logistic regression. Results The study included 834 children (age 13.8 ± 4.1 years, males 46%, body mass index [BMI]: 36.9 ± 7.6 kg/m2; BMI z-score 2.6 ± 0.4). Seventy-four (8.9%) children had TSH between 5 and <10 mIU/L (high TSH [HTSH]). TSH was positively associated with non-high-density lipoprotein (HDL) cholesterol (ß: 1.74; 95% confidence interval [CI] 0.29-3.20, p = 0.02). Total cholesterol and non-HDL cholesterol were higher in males with HTSH compared to those with normal TSH (175.5 vs. 163.5 mg/dL, p = 0.02 and 133.7 vs. 121.4 mg/dL, p = 0.02, respectively). The odds of elevated non-HDL cholesterol (≥145 mg/dL) was higher in males with HTSH relative to those with normal TSH (odds ratio [OR]: 2.78; 95% CI 1.35-5.69, p = 0.005). Conclusions TSH levels were positively associated with non-HDL cholesterol in children with severe obesity. Males with mildly elevated TSH had higher total cholesterol and non-HDL cholesterol compared to males with normal TSH. Further studies are warranted to determine if levothyroxine therapy would result in improvement in total cholesterol or non-HDL cholesterol in children with severe obesity with mildly elevated TSH.


Assuntos
Biomarcadores/sangue , Hipercolesterolemia/etiologia , Hipertireoxinemia/etiologia , Lipídeos/sangue , Obesidade Mórbida/complicações , Tireotropina/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Hipertireoxinemia/sangue , Hipertireoxinemia/diagnóstico , Masculino , Prognóstico , Estudos Retrospectivos
11.
Int J Mol Sci ; 20(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064116

RESUMO

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)-/- mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure-volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Terapia Genética/métodos , Insuficiência Cardíaca/prevenção & controle , Hipercolesterolemia/terapia , Receptores de LDL/genética , Animais , Colesterol/sangue , Dependovirus/genética , Diabetes Mellitus Tipo 2/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/efeitos adversos , Feminino , Insuficiência Cardíaca/fisiopatologia , Hipercolesterolemia/complicações , Hipercolesterolemia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptores de LDL/metabolismo , Volume Sistólico , Fator de Necrose Tumoral alfa/sangue
12.
Nutrients ; 11(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991629

RESUMO

It remains unclear whether cholesterol intake can increase serum cholesterol. Therefore, the present study aimed to investigate the hypothesis that the risk for hypercholesterolemia was not associated with intake of dietary cholesterol after adjusting for saturated fatty acid (SFA). Based on the data from the 2012-2016 KNHANES, dietary cholesterol was positively associated with the risk for abnormalities in total cholesterol (TC) (odds ratio (OR): 1.153, 95% confidence interval (CI): 0.995-1.337; p = 0.028) and low-density lipoprotein cholesterol (LDL-C) (OR: 1.186, 95% CI: 1.019-1.382; p = 0.018) levels before adjusting for SFA; after adjusting for SFA, no significant associations were found between these variables. The mediation analysis showed that dietary cholesterol had no direct effects on the serum levels of TC and LDL-C; in contrast, SFA had significant indirect effects on the association between dietary cholesterol and serum levels of TC and LDL-C. Furthermore, processed meats, but not eggs and other meats, were positively associated with the risk for abnormalities in both TC (OR: 1.220, 95% CI: 1.083-1.374; p = 0.001) and LDL-C (OR: 1.193, 95% CI: 1.052-1.354; p = 0.004) levels. The present study suggested that higher intake of processed meats with high SFA, but not dietary cholesterol was associated with higher risk for abnormalities in TC and LDL-C levels.


Assuntos
Colesterol na Dieta/efeitos adversos , Dieta , Comportamento Alimentar , Hipercolesterolemia/etiologia , Adulto , Colesterol na Dieta/sangue , LDL-Colesterol/sangue , Ingestão de Energia , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Carne , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , República da Coreia
13.
Diabetes Educ ; 45(3): 287-294, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30873908

RESUMO

PURPOSE: The purpose of this study was to examine the collective effect of a symptom cluster (depression, anxiety, fatigue, and impaired sleep quality) at baseline on the quality of life (QOL) of patients with type 2 diabetes (T2DM) over time. METHODS: This was a secondary data analysis of 302 patients with T2DM who presented with both hypertension and hyperlipidemia. All of the participants were enrolled in a randomized controlled intervention study testing strategies to improve medication adherence. The psychological symptoms and QOL were assessed at baseline, 6 months, and 12 months. Cluster analysis was used to identify subgroups of patients based on the severity of symptoms at baseline. RESULTS: Hierarchical cluster analysis identified 4 patient subgroups: all low severity, mild, moderate, and all high severity. There were significant differences in patients' QOL overall among the 4 subgroups. Compared with the all-low-severity subgroup, subgroups with higher severity of the 4 symptoms had poorer QOL across all 3 time points. QOL was most impacted by trait anxiety across the 3 time points. CONCLUSION: QOL was significantly impacted by psychological symptom clusters among patients with T2DM. Healthcare providers should not neglect psychological symptoms that patients experience. It is important to assess and manage these symptoms to improve QOL among patients with diabetes.


Assuntos
Diabetes Mellitus Tipo 2/psicologia , Qualidade de Vida , Índice de Gravidade de Doença , Adulto , Idoso , Ansiedade/etiologia , Análise por Conglomerados , Depressão/etiologia , Diabetes Mellitus Tipo 2/complicações , Fadiga/etiologia , Feminino , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/psicologia , Hipertensão/etiologia , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/psicologia , Síndrome
14.
Circulation ; 139(17): 2032-2048, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30717607

RESUMO

BACKGROUND: Intraplaque hemorrhage promotes atherosclerosis progression, and erythrocytes may contribute to this process. In this study we examined the effects of red blood cells on smooth muscle cell mineralization and vascular calcification and the possible mechanisms involved. METHODS: Erythrocytes were isolated from human and murine whole blood. Intact and lysed erythrocytes and their membrane fraction or specific erythrocyte components were examined in vitro using diverse calcification assays, ex vivo by using the murine aortic ring calcification model, and in vivo after murine erythrocyte membrane injection into neointimal lesions of hypercholesterolemic apolipoprotein E-deficient mice. Vascular tissues (aortic valves, atherosclerotic carotid artery specimens, abdominal aortic aneurysms) were obtained from patients undergoing surgery. RESULTS: The membrane fraction of lysed, but not intact human erythrocytes promoted mineralization of human arterial smooth muscle cells in culture, as shown by Alizarin red and van Kossa stain and increased alkaline phosphatase activity, and by increased expression of osteoblast-specific transcription factors (eg, runt-related transcription factor 2, osterix) and differentiation markers (eg, osteopontin, osteocalcin, and osterix). Erythrocyte membranes dose-dependently enhanced calcification in murine aortic rings, and extravasated CD235a-positive erythrocytes or Perl iron-positive signals colocalized with calcified areas or osteoblast-like cells in human vascular lesions. Mechanistically, the osteoinductive activity of lysed erythrocytes was localized to their membrane fraction, did not involve membrane lipids, heme, or iron, and was enhanced after removal of the nitric oxide (NO) scavenger hemoglobin. Lysed erythrocyte membranes enhanced calcification to a similar extent as the NO donor diethylenetriamine-NO, and their osteoinductive effects could be further augmented by arginase-1 inhibition (indirectly increasing NO bioavailability). However, the osteoinductive effects of erythrocyte membranes were reduced in human arterial smooth muscle cells treated with the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide or following inhibition of NO synthase or the NO receptor soluble guanylate cyclase. Erythrocytes isolated from endothelial NO synthase-deficient mice exhibited a reduced potency to promote calcification in the aortic ring assay and after injection into murine vascular lesions. CONCLUSIONS: Our findings in cells, genetically modified mice, and human vascular specimens suggest that intraplaque hemorrhage with erythrocyte extravasation and lysis promotes osteoblastic differentiation of smooth muscle cells and vascular lesion calcification, and also support a role for erythrocyte-derived NO.


Assuntos
Membrana Eritrocítica , Calcificação Vascular/etiologia , Animais , Aorta , Diferenciação Celular , Células Cultivadas , Durapatita/metabolismo , Guanilato Ciclase/antagonistas & inibidores , Hemorragia/complicações , Humanos , Hipercolesterolemia/etiologia , Camundongos , Camundongos Knockout para ApoE , Miócitos de Músculo Liso/patologia , Neointima/patologia , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/deficiência , Técnicas de Cultura de Órgãos , Osteoblastos/patologia , Triazenos/toxicidade
15.
PLoS One ; 14(1): e0210373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650126

RESUMO

BACKGROUND: Hypercholesterolaemia is common in patients after cardiac transplantation. Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol levels and subsequently the risk of cardiovascular events in patients with dyslipidaemia. There are no published data on the effect of this medication class on cholesterol levels in patients after cardiac transplantation. METHODS: In this retrospective study we investigated patients who were treated with PCSK9 inhibitors either because of intolerance of statins or residual hypercholesterolaemia with evidence of cardiac allograft vasculopathy. We compared the data of patients prior to the start with these medications with their most recent dataset. RESULTS: Ten patients (nine men; mean age 58±6 years) underwent cardiac transplantation 8.3±4.5 (range 3-15) years ago. The treatment duration of Evolocumab or Alirocumab was on average 296±125 days and lead to a reduction of total Cholesterol (281±52 mg/dl to 197±36 mg/dl; p = 0.002) and LDL Cholesterol (170±22 mg/dl to 101±39 mg/dl; p = 0.001). No significant effects on HDL Cholesterol, BNP, Creatin Kinase or hepatic enzymes were noticed. There were no unplanned hospitalisations, episodes of rejections, change of ejection fraction or opportunistic infections. Both patients on Alirocumab developed liver pathologies: One patient died of hepatocellular carcinoma and the other developed hepatitis E. CONCLUSIONS: Our study demonstrates that the PCSK9 inhibitors Evolocumab and Alirocumab lead to a significant reduction of LDL Cholesterol in heart transplantation recipients. No effect on cardiac function or episodes of rejections were noticed. Larger and long-term studies are needed to establish safety and efficacy of PCSK9 inhibitors after cardiac transplantation.


Assuntos
Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Feminino , Transplante de Coração/efeitos adversos , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores de Serino Proteinase/efeitos adversos
16.
BJOG ; 126(1): 33-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30144277

RESUMO

OBJECTIVE: To assess the association between the outcome of a woman's first pregnancy and risk of clinical cardiovascular disease risk factors. DESIGN: Prospective cohort study. SETTING AND POPULATION: Nurses' Health Study II. METHODS: Multivariable-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between first pregnancy outcome and hypertension, type 2 diabetes, and hypercholesterolemia. MAIN OUTCOME MEASURES: Hypertension, type 2 diabetes, and hypercholesterolemia. RESULTS: Compared to women who reported a singleton live first birth, women with early spontaneous abortion (<12 weeks) had a greater rate of type 2 diabetes (HR: 1.20; 95% CI: 1.07-1.34) and hypercholesterolemia (HR: 1.06; 95% CI: 1.02-1.10), and a marginally increased rate of hypertension (HR: 1.05, 95% CI: 1.00-1.11). Late spontaneous abortion (12-19 weeks) was associated with an increased rate of type 2 diabetes (HR: 1.38; 95% CI: 1.14-1.65), hypercholesterolemia (HR: 1.11; 95% CI: 1.03-1.19), and hypertension (HR: 1.15; 95% CI: 1.05-1.25). The rates of type 2 diabetes (HR: 1.45; 95% CI: 1.13-1.87) and hypertension (HR: 1.15; 95% CI: 1.01-1.30) were higher in women who delivered stillbirth. In contrast, women whose first pregnancy ended in an induced abortion had lower rates of hypertension (HR: 0.87; 95% CI: 0.84-0.91) and type 2 diabetes (HR: 0.89; 95% CI: 0.79-0.99) than women with a singleton live birth. CONCLUSIONS: Several types of pregnancy loss were associated with an increased rate of hypertension, type 2 diabetes, and hypercholesterolemia, which may provide novel insight into the pathways through which pregnancy outcomes and CVD are linked. TWEETABLE ABSTRACT: Pregnancy loss is associated with later maternal risk of hypertension, type 2 diabetes, and hypercholesterolemia.


Assuntos
Aborto Espontâneo/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Resultado da Gravidez/epidemiologia , Natimorto/epidemiologia , Aborto Induzido/estatística & dados numéricos , Adulto , Intervalos de Confiança , Diabetes Mellitus Tipo 2/etiologia , Feminino , Idade Gestacional , Humanos , Hipercolesterolemia/etiologia , Hipertensão/etiologia , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
17.
FASEB J ; 33(1): 1110-1123, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113880

RESUMO

Epidemiologic studies showed that low birth weight is associated with high cholesterol and an increased risk of cardiovascular diseases in adulthood. This study aimed to elucidate the intrauterine programming mechanisms of adult hypercholesterolemia. The results showed that prenatal nicotine exposure (PNE) caused intrauterine growth retardation and hypercholesterolemia in male adult offspring rats. Hepatic cholesterol synthesis and output were deceased in utero but increased in adults; hepatic reverse cholesterol transport (RCT) persistently deceased before and after birth. Meanwhile, PNE elevated serum corticosterone level and decreased hepatic IGF1 pathway activity in male fetuses, whereas converse changes were observed in male adults. The chronic stress model and cortisol-treated HepG2 cells verified that excessive glucocorticoid (GC)-induced GC-IGF1 axis programming enhanced hepatic cholesterol synthesis and output. In addition, PNE decreased the expression of specific protein 1 and P300 enrichment and H3K27 acetylation at the promoter region of genes responsible for RCT both in fetal and adult, male livers and reduced expression of those genes, similar alterations were also confirmed in cortisol-treated HepG2 cells, suggesting that excessive GC-related programming induced continuous RCT reduction by epigenetic modification. Taken together, the "2-programming" approach discussed above may ultimately contribute to the development of hypercholesterolemia in male adult offspring.-Zhou, J., Zhu, C., Luo, H., Shen, L., Gong, J., Wu, Y., Magdalou, J., Chen, L., Guo, Y., Wang, H. Two intrauterine programming mechanisms of adult hypercholesterolemia induced by prenatal nicotine exposure in male offspring rats.


Assuntos
Desenvolvimento Fetal , Hipercolesterolemia/etiologia , Nicotina/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Acetilação , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/biossíntese , Colesterol/sangue , Colesterol/metabolismo , Corticosterona/sangue , Feminino , Células Hep G2 , Histonas/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/efeitos dos fármacos , Fígado/embriologia , Fígado/metabolismo , Masculino , Nicotina/administração & dosagem , Gravidez , Ratos , Ratos Wistar , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/metabolismo
18.
Intern Med ; 58(3): 345-353, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30210130

RESUMO

Objective The aim of this study was to assess the relationship between hypercholesterolemia (HC) and clinical events through a percutaneous coronary intervention (PCI) registry. HC is a well-known independent risk factor for long-term cardiovascular events after PCI. However, it has been reported to be associated with a lower risk of adverse events in patients with cancer or acute coronary syndrome. Methods We analyzed the relationship between HC and adverse events in patients treated with everolimus-eluting stents (EESs) through the Tokyo-MD PCI study (an all-comer, multicenter, observational registry). The propensity score method was applied to select two groups with similar baseline characteristics. Results The unadjusted population included 1,536 HC patients and 330 non-HC patients. Propensity score matching yielded 314 matched pairs. After baseline adjustment, the outcomes of HC patients were significantly better than those of the non-HC patients with respect to the primary endpoint, which was a combination of mortality from all causes, nonfatal myocardial infarction (MI), nonfatal neurological events, and major bleeding [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39-0.81; p=0.002], and the secondary endpoints, which included a combination of mortality from all causes, nonfatal MI, and nonfatal neurological events (HR 0.59, 95% CI 0.39-0.88; p=0.01), and major bleeding (HR 0.42, 95% CI 0.20-0.88; p=0.02). A subgroup analysis showed age as an interaction factor for the primary endpoint (interaction p=0.035). Conclusion HC was associated with better outcomes in patients who underwent EES implantation, even after baseline adjustment.


Assuntos
Síndrome Coronariana Aguda/etiologia , Stents Farmacológicos/efeitos adversos , Hipercolesterolemia/etiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Tóquio , Resultado do Tratamento
19.
Behav Brain Res ; 359: 648-656, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30287273

RESUMO

While chronic high-fat feeding has long been associated with the rising incidence of obesity/type 2 diabetes, recent evidence has established that it is also associated with deficits in hippocampus-dependent memory. In this regard, environmental enrichment (EE) is an animal housing technique composed of increased space, physical activity, and social interactions, which in turn increases sensory, cognitive, motor, and social stimulation. EE leads to improved cerebral health as defined by increased neurogenesis, enhanced learning and memory and resistance to external cerebral insults. In the present study, the impacts of environmental enrichment (EE) on Swiss mice fed a high-fat, cholesterol-enriched diet (HFECD; 20% fat and 1.5% cholesterol) were investigated. Here, we demonstrated that EE, when initiated 4 weeks after the beginning of HFECD in mice, prevents HFECD-induced spatial memory and object recognition impairment, which were tested in T-maze and object recognition tests. Although EE did not affect HFECD-induced weight gain or hypercholesterolaemia, it improved glucose tolerance. On the other hand, EE was unable to mitigate a decrease in brain-derived neurotrophic factor (BDNF) and IL-6 hippocampal levels induced by the HFECD. Overall, while our results reinforce the positive and neuroprotective effects of EE on cognition they do not support a role for EE in preventing the neurochemical changes induced by the HFECD. Based on clinical observations that nondiabetic individuals with mild forms of impaired glucose tolerance have a higher risk of cognitive impairments, one can speculate about the connection between the effects of EE on glucose intolerance and its effects on cognition.


Assuntos
Colesterol/efeitos adversos , Disfunção Cognitiva/terapia , Dieta Hiperlipídica/efeitos adversos , Meio Ambiente , Abrigo para Animais , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Intolerância à Glucose/terapia , Hipocampo/metabolismo , Hipocampo/patologia , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hipercolesterolemia/psicologia , Interleucina-6/metabolismo , Masculino , Camundongos , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/psicologia , Distribuição Aleatória , Memória Espacial
20.
Arch Physiol Biochem ; 125(3): 220-227, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29544357

RESUMO

High fat diet (HFD) exposure is associated with various pathological dysfunctions, including haematological disorders and oxidative stress. The in vitro analysis of AECG revealed the presence of important levels of polyphenols and flavonoids, and denoted antioxidant capacities confirmed by nitric oxide radical (NO•), reducing the power and HPLC chemical components' determinations. The animals exposed to HFD revealed a severe damage in the blood cells structure and haematological parameters accompanied with a significant decrease in serum Mg2+ and Ca2+ ATPase activities. Furthermore, malondialdehyde (MDA) and the advanced oxidation of protein products (AOPP) levels were significantly increased, while vitamin C level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were markedly reduced in the erythrocytes and platelets of HFD-treated mice. However, the co-administration of AECG with HFD-treated animals restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Chaetomorpha gracilis extract was a useful element preventing HFD-induced blood cells damage.


Assuntos
Clorófitas/química , Eritrócitos/efeitos dos fármacos , Hipercolesterolemia/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Eritrócitos/patologia , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Oxirredução , Superóxido Dismutase/metabolismo
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