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1.
J Sci Food Agric ; 100(2): 846-854, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31646650

RESUMO

BACKGROUND: Pomegranate has antioxidant, cardioprotective and anti-inflammatory properties. We designed a crossover study aimed at determining if consumption of pomegranate juice (PJ) improves lipid profile and oxidative and inflammatory biomarkers of hemodialysis patients. Forty-one hemodialysis patients were randomly assigned to one of two groups: PJ-treated group receiving 100 mL of natural PJ immediately after their dialysis session three times a week and the control group receiving the usual care. After 8 weeks, a 4-week washout period was established and then the role of the groups was exchanged. Lipid profile, blood pressure and oxidative and inflammatory biomarkers were measured before and after each sequence. RESULTS: Based on the results of intention-to-treat analysis, triglycerides were decreased in PJ condition and increased in the controls. Conversely, high-density lipoprotein cholesterol was increased in PJ and decreased in the control group. Total and low-density lipoprotein cholesterol did not significantly change in either condition. Systolic and diastolic blood pressure significantly decreased in PJ condition. Total antioxidant capacity increased in PJ condition (P < 0.001) and decreased in the controls (P < 0.001). Conversely, malondialdehyde and interleukin-6 decreased in PJ (P < 0.001) and increased in the control group (P ≤ 0.001). The changes of these biomarkers were significantly different between the two conditions. CONCLUSIONS: Eight-week PJ consumption showed beneficial effects on blood pressure, serum triglycerides, high-density lipoprotein cholesterol, oxidative stress and inflammation in hemodialysis patients. © 2019 Society of Chemical Industry.


Assuntos
Doenças Cardiovasculares/metabolismo , Sucos de Frutas e Vegetais/análise , Insuficiência Renal Crônica/dietoterapia , Adulto , Idoso , Pressão Sanguínea , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Estudos Cross-Over , Feminino , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia , Triglicerídeos/metabolismo
4.
Vasc Health Risk Manag ; 15: 309-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692533

RESUMO

Experimentally induced injury triggers up-regulation and mobilization of stem cells in Apoe -/- mice that causes accelerated atherosclerosis. Abca1 -/- Abcg1-/- mice have chronic activation of stem cell up-regulation/mobilization and accelerated atherosclerosis. In addition, the Abca1 -/- Abcg1-/- mice have elevation of serum cytokines G-CSF, IL-17 and IL-23, each necessary for stem cell mobilization. IL-17 and IL-23 are elevated in two human illnesses that have cardiovascular (CV) risk independent of traditional risk factors-SLE and psoriasis. Serum G-CSF, which can be elevated in liver disease, predicts major adverse cardiovascular events in humans. These serum cytokine elevations suggest activation of the stem cell mobilization mechanism in humans that results, as in mice, in accelerated atherosclerosis. Efforts to reduce CV disease in these patient populations should include mitigation of the diseases that trigger stem cell mobilization. Since activation of the stem cell up-regulation/mobilization mechanism appears to accelerate human atherosclerosis, use of stem cells as therapy for arterial occlusive disease should distinguish between direct administration of stem cells and activation of the stem cell up-regulation/mobilization mechanism.


Assuntos
Doenças Cardiovasculares/patologia , Movimento Celular , Hepatopatias/patologia , Psoríase/patologia , Células-Tronco/patologia , Transportador 1 de Cassete de Ligação de ATP/deficiência , Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Modelos Animais de Doenças , Progressão da Doença , Humanos , Mediadores da Inflamação/metabolismo , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/terapia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Camundongos Knockout para ApoE , Fenótipo , Prognóstico , Psoríase/genética , Psoríase/metabolismo , Psoríase/terapia , Fatores de Risco , Células-Tronco/metabolismo
5.
Anal Bioanal Chem ; 411(29): 7725-7735, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760445

RESUMO

The rapid and simultaneous detection of DNA and protein biomarkers is necessary to detect the outbreak of a disease or to monitor a disease. For example, cardiovascular diseases are a major cause of adult mortality worldwide. We have developed a rapidly adaptable platform to assess biomarkers using a microfluidic technology. Our model mimics autoantibodies against three proteins, C-reactive protein (CRP), brain natriuretic peptide (BNP), and low-density lipoprotein (LDL). Cell-free mitochondrial DNA (cfmDNA) and DNA controls are detected via fluorescence probes. The biomarkers are covalently bound on the surface of size- (11-15 µm) and dual-color encoded microbeads and immobilized as planar layer in a microfluidic chip flow cell. Binding events of target molecules were analyzed by fluorescence measurements with a fully automatized fluorescence microscope (end-point and real-time) developed in house. The model system was optimized for buffers and immobilization strategies of the microbeads to enable the simultaneous detection of protein and DNA biomarkers. All prime target molecules (anti-CRP, anti-BNP, anti-LDL, cfmDNA) and the controls were successfully detected both in independent reactions and simultaneously. In addition, the biomarkers could also be detected in spiked human serum in a similar way as in the optimized buffer system. The detection limit specified by the manufacturer is reduced by at least a factor of five for each biomarker as a result of the antibody detection and kinetic experiments indicate that nearly 50 % of the fluorescence intensity is achieved within 7 min. For rapid data inspection, we have developed the open source software digilogger, which can be applied for data evaluation and visualization. Graphical abstract.


Assuntos
Doenças Cardiovasculares/metabolismo , Ácidos Nucleicos Livres/análise , Dispositivos Lab-On-A-Chip , Proteínas/análise , Autoanticorpos/análise , Biomarcadores/análise , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Microesferas , Proteínas/imunologia
6.
Methodist Debakey Cardiovasc J ; 15(3): 200-206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687099

RESUMO

Nitric oxide (NO) is continually produced by the enzyme nitric oxide synthase (NOS) and is essential to the control and effectiveness of the cardiovascular system. However, there is a substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular complications. Fortunately, NO can also be produced by the sequential reduction of inorganic nitrate to nitrite and then to NO. Nitric oxide from inorganic nitrate supplementation has been found to have the same cardioprotective benefits of NO produced by NOS. Moreover, it can effectively compensate for declining NOS activity due to aging or NOS inhibition by oxidative stress, hypoxia, or other factors. This review covers some of the major cardiovascular regulatory actions of NO and presents evidence that NO from inorganic nitrate supplementation can provide (1) compensation when NOS activity is inadequate, and (2) cardioprotective benefits beyond that provided by a healthy NOS system. In addition, it discusses how to obtain a safe and efficacious range of inorganic nitrate.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Suplementos Nutricionais , Nitratos/uso terapêutico , Óxido Nítrico/metabolismo , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Nível de Saúde , Humanos , Nitratos/efeitos adversos , Óxido Nítrico Sintase/metabolismo , Fatores de Risco , Resultado do Tratamento
7.
J Clin Pathol ; 72(12): 785-799, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31611285

RESUMO

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.


Assuntos
Líquidos Corporais/metabolismo , Doenças Cardiovasculares/diagnóstico , Técnicas de Diagnóstico Molecular , Medicina de Precisão , Biomarcadores/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Ácidos Nucleicos Livres/sangue , Tomada de Decisão Clínica , Humanos , Biópsia Líquida , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
9.
Rev Cardiovasc Med ; 20(3): 153-160, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601089

RESUMO

Exosomes, nanosized lipid bilayer membranous vesicles, are secreted by a variety of cells and contain protein, lipids, mRNA, miRNA, and signaling molecules that participate in intercellular material transfer and information exchange through binding, fusion or endocytosis. Exosomes mediate the gene expression of target cells and regulate pathological and physiological processes, thereby playing a key role in the occurrence and development of various diseases. Accumulated studies has shown that exosomes hold therapeutic potential though their anti-apoptotic and anti-fibrotic roles. They also have been shown to promote angiogenesis, inhibit ventricular remodeling and improve cardiac function, as well as inhibiting local inflammation and regulating the immune response. As such, exosomes represent a new target for the treatment of cardiovascular diseases. This review summarizes the literature in this field to date, including the basic biological characteristics of exosomes, and new progress in the understanding of the mechanisms of their involvement in immune regulation in cardiovascular diseases. In this way, it servrs as a basis for future research and the development of therapeutic exosomes.


Assuntos
Doenças Cardiovasculares/imunologia , Sistema Cardiovascular/imunologia , Exossomos/imunologia , Sistema Imunitário/imunologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Exossomos/metabolismo , Exossomos/transplante , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Prognóstico , Transdução de Sinais
11.
Clin Interv Aging ; 14: 1589-1599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564841

RESUMO

Purpose: To explore the effects of 10 weeks of progressive vigorous interval training as a single intervention on health-related quality of life (HRQoL) and cardiometabolic risk markers in centrally obese 70-year-old individuals. Participants and methods: A randomized controlled trial (ClinicalTrials.gov registration no. NCT03450655) including seventy-seven community-dwelling 70-year-old men and women with central obesity defined as > 1 kg visceral adipose tissue for women and > 2 kg for men. Participants randomized to the intervention group were offered a 10-week progressive vigorous interval training program performed three times per week. Control subjects were asked to maintain their daily living and routines throughout the trial. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. Prespecified outcome measures included: changes in HRQoL using the Short Form Health Survey Questionnaire (SF-36), blood pressure; resting heart rate (HR) and blood lipids. All analyses were conducted on an intention-to-treat basis. Results: The intervention resulted in significant effects on the SF-36 mental component summary (MCS) score and the mental health (MH) subscale (P< 0.05 for both), when compared to the control group. Specifically, the intervention group increased their MCS score by 6.3 points (95% confidence interval [CI] = 0.3-12.3) and their MH score by 6.0 points (95% CI = 1.7-10.4) compared to the control group. Moreover, significant effects were seen on resting HR, total cholesterol and LDL-cholesterol (P<0.05 for all). Conclusion: It was shown that 10 weeks of vigorous interval training as a single intervention was sufficient to improve mental aspects of HRQoL in older individuals with central obesity, which is a critical aspect of healthy ageing. Positive effects were seen also on cardiometabolic risk markers.


Assuntos
Doenças Cardiovasculares/metabolismo , Exercício/psicologia , Obesidade/terapia , Qualidade de Vida/psicologia , Circunferência da Cintura , Idoso , Doenças Cardiovasculares/prevenção & controle , Exercício/fisiologia , Feminino , Humanos , Vida Independente , Masculino , Inquéritos e Questionários , Resultado do Tratamento
12.
J Agric Food Chem ; 67(44): 12191-12198, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588747

RESUMO

Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Alho/química , Extratos Vegetais/administração & dosagem , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Espectrometria de Massas , Metabolômica , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
13.
Anticancer Res ; 39(9): 4627-4635, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519560

RESUMO

In the clinical setting, administration of high daily or bolus doses of vitamin D is often solely based on 25-hydroxyvitamin D [25(OH)D] testing. This review summarizes the evidence of the effect of vitamin D on cardiovascular disease (CVD). Meta-analyses of randomized controlled trials (RCTs) have demonstrated that CVD risk markers, such as lipid parameters, inflammation markers, blood pressure, and arterial stiffness, are largely unaffected by vitamin D supplementation. Similar results have been obtained regarding CVD events and mortality from (meta)-analyses of RCTs, even in subgroups with 25(OH)D concentrations <50 nmol/l. Likewise, Mendelian randomization studies have indicated that the genetic reduction of the 25(OH)D concentration does not increase CVD risk. Some studies do not exclude the possibility of adverse vitamin D effects, such as elevated plasma calcium concentration and an increased CVD risk at a 25(OH)D concentration >125 nmol/l. Based on a conservative benefit-risk management approach, vitamin D doses beyond the nutritionally recommended amounts of 600 to 800 IE daily currently cannot be advised for the prevention of CVD events.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Vitamina D/metabolismo , Animais , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais/efeitos adversos , Overdose de Drogas/complicações , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico
14.
Toxicol Lett ; 317: 13-23, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31562912

RESUMO

Combination antiretroviral therapy (cART) has been hugely successful in reducing the mortality associated with human immunodeficiency virus (HIV) infection, resulting in a growing population of people living with HIV (PLWH). Since PLWH now have a longer life expectancy, chronic comorbidities have become the focus of the clinical management of HIV. For example, cardiovascular complications are now one of the most prevalent causes of death in PLWH. Numerous epidemiological studies show that antiretroviral treatment increases cardiovascular disease (CVD) risk and early onset of CVD in PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and two NRTIs are typically used in combination with one drug from another drug class, e.g., a fusion inhibitor. NRTIs are known to induce mitochondrial dysfunction, contributing to toxicity in numerous tissues, such as myopathy, lipoatrophy, neuropathy, and nephropathy. In in vitro studies, short-term NRTI treatment induces an endothelial dysfunction with an increased reactive oxygen species (ROS) production; long-term NRTI treatment decreases cell replication capacity, while increasing mtROS production and senescent cell accumulation. These findings suggest that a mitochondrial oxidative stress is involved in the pathogenesis of NRTI-induced endothelial dysfunction and premature senescence. Mitochondrial dysfunction, defined by a compromised mitochondrial quality control via biogenesis and mitophagy, has a causal role in premature endothelial senescence and can potentially initiate early cardiovascular disease (CVD) development in PLWH. In this review, we explore the hypothesis and present literature supporting that long-term NRTI treatment induces vascular dysfunction by interfering with endothelial mitochondrial homeostasis and provoking mitochondrial genomic instability, resulting in premature endothelial senescence.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Senescência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Animais , Fármacos Anti-HIV/administração & dosagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Esquema de Medicação , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Metabolismo Energético/efeitos dos fármacos , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
15.
Nat Commun ; 10(1): 4329, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551469

RESUMO

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10-8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.


Assuntos
Doenças Cardiovasculares/metabolismo , Lipídeos/genética , Plasma/metabolismo , Doenças Cardiovasculares/genética , Estudo de Associação Genômica Ampla , Humanos
16.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(7): 402-409, ago.-sept. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-182859

RESUMO

Background: This study was designed to detect the potential association of a nonfunctional adrenal incidentaloma (NFAI) with insulin resistance and associated metabolic disturbances, with a subsequent increase in cardiovascular risk factors. Methods: Eighty-three NFAI patients and 56 volunteers (controls) without any adrenal abnormalities on computed tomography (CT) were included. Fasting blood glucose (FBG), fasting insulin, lipid profiles, uric acid, homocysteine, fibrinogen, high sensitivity C-reactive protein (hs-CRP), and adiponectin levels were measured in both groups. Blood pressure (BP), waist circumference, body mass index (BMI), and carotid intima media thickness (CIMT) were evaluated in both the patients and volunteers. Results: There were no significant difference between the NFAI and control groups with respect to age, sex, BMI, waist circumference, systolic and diastolic BP, smoking, concomitant disease, and medications. Fasting insulin and glucose levels and homeostasis model of assessment-insulin resistance (HOMA-IR) scores were significantly higher in the NFAI group as compared with those in the control group (p<0.01). The frequency of metabolic syndrome in the NFAI group was higher than that in the control group (p<0.01). All the lipid fractions, except triglyceride (TG), (p<0.05), homocysteine (p=0.01), and fibrinogen levels (p<0.001), were significantly higher in the NFAI group as compared with the levels in the control group. There were no significant differences between the NFAI and control groups in terms of uric acid, hs-CRP, and adiponectin levels. The CIMT values in the NFAI group were significantly higher than those in the control group (0.74±0.14 vs. 0.53±0.09, p<0.001). The mean CIMT value showed a statistically positive correlation with age (r=0.245, p=0.004); the HOMA-IR score (r=0.490, p<0.001); and FBG (r=0.521, p<0.001), fasting insulin (r=0.432, p<0.001), total cholesterol (TC) (r=0.267, p=0.002), and fibrinogen (r=0.398, p<0.001) levels in the NFAI group. Conclusions: The results indicated that the NFAI patients had an elevated risk of insulin resistance, with metabolic syndrome and increased CIMT values. Long-term follow-up studies should be designed to evaluate postsurgical alterations in metabolic parameters and cardiovascular risk factors in NFAI patients


Antecedentes: Este estudio se diseñó para detectar la posible asociación del incidentaloma suprarrenal no funcionante (ISNF) con resistencia a la insulina y trastornos metabólicos asociados, con un incremento subsecuente en los factores de riesgo cardiovascular. Métodos: Se incluyó a 83 pacientes con ISNF y a 56 voluntarios (controles) sin anomalías suprarrenales en la tomografía computarizada (TC). Se determinaron en ambos grupos los valores de glucemia en ayunas (GA), insulina en ayunas, perfiles lipídicos, ácido úrico, homocisteína, fibrinógeno, proteína C reactiva de alta sensibilidad (PCRas) y adiponectina. Se evaluaron la presión arterial (PA), el perímetro de la cintura, el índice de masa corporal (IMC) y el grosor íntima-media carotídea (GIMC) tanto en los pacientes como en los voluntarios. Resultados: No había una diferencia significativa entre los grupos con ISNF y de control en cuanto a edad, sexo, IMC, perímetro de la cintura, PA sistólica y diastólica, tabaquismo, enfermedades concomitantes y medicamentos. Las concentraciones de insulina y glucosa en ayunas y las puntuaciones del modelo homeostático de evaluación de la resistencia a la insulina (HOMA-IR) fueron significativamente mayores en el grupo con ISNF que en el de control (p<0,01). La frecuencia de síndrome metabólico fue mayor en el grupo con ISNF que en el de control (p<0,01). Los valores de todas las fracciones lipídicas, excepto los de triglicéridos (TG) (p<0,05), homocisteína (p=0,01) y fibrinógeno (p<0,001), fueron significativamente mayores en el grupo con ISNF que en el de control. No hubo diferencias significativas entre los grupos con ISNF y de control en las concentraciones de ácido úrico, PCRas y adiponectina. Los valores del GIMC en el grupo con ISNF fueron significativamente mayores que los del grupo de control (0,74±0,14 frente a 0,53±0,09; p<0,001). El valor medio del GIMC mostró una correlación estadísticamente positiva con la edad (r=0,245; p=0,004); la puntuación del HOMA-IR (r=0,490; p<0,001), y la GA (r=0,521; p<0,001), la insulina en ayunas (r=0,432; p<0,001), el colesterol total (CT) (r=0,267; p=0,002) y el fibrinógeno (r=0,398; p<0,001) en el grupo con ISNF. Conclusión: Los resultados indicaban que los pacientes con ISNF tenían un riesgo elevado de resistencia a la insulina, con síndrome metabólico y aumento de los valores del GIMC. Deben diseñarse estudios de seguimiento a largo plazo para evaluar los cambios posquirúrgicos de los parámetros metabólicos y los factores de riesgo cardiovascular en pacientes con ISFN


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Achados Incidentais , Fatores de Risco , Neoplasias das Glândulas Suprarrenais/complicações , Doenças Cardiovasculares/metabolismo , Espessura Intima-Media Carotídea , Síndrome Metabólica/complicações , Resistência à Insulina , Glândulas Suprarrenais/patologia , Síndrome Metabólica/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Doenças Cardiovasculares/complicações , Síndrome Metabólica/fisiopatologia , Voluntários Saudáveis , Pressão Arterial , Índice de Massa Corporal , Relação Cintura-Quadril
17.
Arq. bras. cardiol ; 113(2 supl.1): 251-251, set., 2019.
Artigo em Português | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1021277

RESUMO

INTRODUÇÃO: A busca na melhoria da terapêutica da insuficiência cardíaca (IC) é desafio contínuo. Assim, novos fármacos, como o sacubitril-valsartana (SV), surgiram com indícios promissores através de resultados iniciais positivos na redução de mortalidade e reinternação hospitalar. Neste sentido, a mensuração efetiva das respostas cardiometabólicas (CM) torna-se imprescindível na sedimentação desse tratamento farmacológico e de sua análise em diversas etiologias da síndrome da IC. OBJETIVO: Analisar as respostas CM ao uso de SV em pacientes portadores de IC avançada através do teste cardiopulmonar de exercício (TCPE) e possibilitar avaliação funcional e prognóstica individualizada. MÉTODOS: Coorte de pacientes que iniciaram uso de SV durante acompanhamento ambulatorial de IC. Incluídos os pacientes avaliados com TCPE antes e após 8 ± 4,3 meses do início da terapia com SV em diversas etiologias da IC: Isquêmica, Chagásica, Valvar, Idiopática e outras. Analisados parâmetros clínicos (Classe Funcional (CF) ­ NYHA), CM através do VO2 pico, % do VO2 máx predito, Eficiência Metabólica (OUES), Tempo de queda do VO2 (T1/2) além da eficiência ventilatória (VE/VCO2 slope). RESULTADOS: Nesse estudo inicial com 8 pacientes onde 50% em CF III da NYHA, 75% cursaram com melhora da CF e piora em 25%. Houve tendência a melhor eficiência metabólica (OUES) e do T1/2 (p>0,05) e acréscimo significativo do VO2pico de 20,63 ± 4,6 para 23,22 ± 5,65 (p=0,012). A relação VE/VCO2 slope tendeu a redução de 36,8 ± 4,9 para 34,0 ± 8,3 (p>0,05). CONCLUSÕES: A terapia com SV promoveu redução expressiva da CF e incremento significativo na potência aeróbica (VO2 pico) em pacientes com IC e CF II/III. Houve tendência à melhora da eficiência metabólica e ventilatória no grupo estudado. Os portadores de miocardiopatia chagásica deste grupo não obtiveram melhora de CF. O TCPE foi ferramenta fundamental na avaliação funcional e resposta terapêutica de pacientes com IC de diversas de etiologias. (AU)


Assuntos
Humanos , Doenças Cardiovasculares/metabolismo , Insuficiência Cardíaca , Valsartana
19.
Curr Top Med Chem ; 19(20): 1818-1849, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456521

RESUMO

Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Nefropatias/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Nefropatias/metabolismo
20.
Physiol Rev ; 99(4): 1819-1875, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31434538

RESUMO

Metabolomics uses advanced analytical chemistry techniques to enable the high-throughput characterization of metabolites from cells, organs, tissues, or biofluids. The rapid growth in metabolomics is leading to a renewed interest in metabolism and the role that small molecule metabolites play in many biological processes. As a result, traditional views of metabolites as being simply the "bricks and mortar" of cells or just the fuel for cellular energetics are being upended. Indeed, metabolites appear to have much more varied and far more important roles as signaling molecules, immune modulators, endogenous toxins, and environmental sensors. This review explores how metabolomics is yielding important new insights into a number of important biological and physiological processes. In particular, a major focus is on illustrating how metabolomics and discoveries made through metabolomics are improving our understanding of both normal physiology and the pathophysiology of many diseases. These discoveries are yielding new insights into how metabolites influence organ function, immune function, nutrient sensing, and gut physiology. Collectively, this work is leading to a much more unified and system-wide perspective of biology wherein metabolites, proteins, and genes are understood to interact synergistically to modify the actions and functions of organelles, organs, and organisms.


Assuntos
Metabolismo Energético , Metaboloma , Metabolômica/métodos , Animais , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Humanos , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Erros Inatos do Metabolismo/metabolismo , Erros Inatos do Metabolismo/fisiopatologia , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Fluxo de Trabalho
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