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1.
Ann Hematol ; 99(2): 359-361, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872359
2.
Mayo Clin Proc ; 94(12): 2455-2466, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31806099

RESUMO

OBJECTIVE: To investigate the factors that are associated with the effect of metformin on endothelial dysfunction in polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: From March 24, 2014, to November 18, 2016, 48 women with PCOS were randomly assigned to 1500 mg/d of metformin (N=29) or no treatment (N=13) for 3 months; 42 patients (29 in the initial treatment group and 13 in the no treatment group) completed the study. Study variables were measured at baseline and after 3 months. Participants who did not receive metformin initially were then treated with metformin for another 3 months, and study variables were measured again. Endothelial function was measured as reactive hyperemia-peripheral arterial tonometry (RH-PAT) from the index finger. RESULTS: The age and baseline endothelial function (mean ± SD) of the participants were 32.7±6.9 years and 1.8±0.5, respectively. No notable change was observed in endothelial function after 3 months with metformin compared with no treatment. However, after stratifying participants who received metformin based on baseline endothelial function, there was a significant improvement following metformin treatment in participants with abnormal baseline endothelial function (1.3±0.3 vs 1.7±0.3; P<.001) but not in those with normal baseline endothelial function (2.1±0.4 vs 2.0±0.5; P=.11). CONCLUSION: Metformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. Metformin has a direct effect on endothelial function in PCOS, and measurement of endothelial function can stratify and follow response to metformin treatment in PCOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02086526.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Feminino , Humanos , Manometria , Síndrome do Ovário Policístico/fisiopatologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
3.
Medicine (Baltimore) ; 98(49): e18134, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804323

RESUMO

BACKGROUND: Essential hypertension is one of the most common chronic diseases in the world and a major risk factor for cardiovascular and cerebrovascular diseases. Hypertension often leads to a variety of complications, of which vascular endothelial dysfunction is an important part. Traditional Chinese medicine (TCM) combined with western medicine can significantly improve vascular endothelial function in patients with hypertension, but it has not been systematically evaluated for efficacy and safety of essential hypertension. Therefore, we aim to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCM combined with western medicine in improving vascular endothelial function in patients with essential hypertension. METHODS: We will search PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, China Science Journal Database (VIP Database) and China Biomedical Literature Database (CBM). Clinical trial registrations, potential grey literature, related conference abstracts, and reference lists of identified studies will also be retrieved. The electronic database will be searched for literatures published from the beginning to October 2018. Based on the heterogeneity test, data integration is performed using a fixed effect model or a random effects model. Changes in blood pressure and endothelial function will be assessed as primary outcomes. Drug use, disease progression and adverse events will be assessed as secondary outcomes. RevMan V.5.3.5 will be used for meta-analysis. RESULTS: This systematic review and meta-analysis will provide high-quality evidence from a variety of aspects, including efficacy, blood pressure, vascular endothelial function and adverse reactions, to assess the efficacy and safety of TCM combined with western medicine in patients with hypertension. CONCLUSION: This systematic review will determine whether TCM combined with western medicine provides evidence for effective intervention of vascular endothelial function in patients with essential hypertension. ETHICS AND DISSEMINATION: This systematic review and meta-analysis of randomized controlled trials does not require ethical recognition, and the results of this paper will be published in an open access, internationally influential academic journal. PROSPERO REGISTRATION NUMBER: CRD42019140743.


Assuntos
Anti-Hipertensivos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Hipertensão Essencial/tratamento farmacológico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
4.
Int Heart J ; 60(6): 1421-1429, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735774

RESUMO

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE-/-) mice. Eight-week-old nondiabetic ApoE-/- mice fed a Western-type diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE-/- mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE-/- mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.


Assuntos
Aterosclerose/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Vildagliptina/uso terapêutico , Animais , Apolipoproteínas E , Aterosclerose/etiologia , Aterosclerose/patologia , Técnicas de Cultura de Células , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Endotélio Vascular/patologia , Camundongos , Camundongos Endogâmicos C57BL , Molécula 1 de Adesão de Célula Vascular/sangue
5.
Life Sci ; 238: 116981, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639394

RESUMO

AIM: Endothelial cell damage is critical to understand since its presence in the entire body makes the damage widespread instead of being localized. Being a major component of stem cell niche in bone marrow, deems it essential to gain knowledge of the damage to endothelium associated with bone marrow. Since radiation exposure has become common to numerous therapeutic modalities, its effects on bone marrow and its endothelial cells are crucial to understand. MATERIAL & METHODS: Microarray analysis was performed on irradiated human bone marrow endothelial cells (hBMECs) with and without prior treatment with radioprotectant amifostine to assess the effects of radiation on signalling pathways and the subsequent changes in pathways when treated with radioprotectant prior to radiation exposure. KEY FINDINGS: It was seen that adhesion pathways that were usually inactivated under normal circumstances were stimulated post radiation. However, where in the case of radiation exposure, these adhesion pathways included leukocyte adhesion and migration; in the case of radioprotected conditions the pathways revolve around cell-substrate adhesion and cell spreading. Genes like ROCK1, FLNA, RAC1, PRKCZ and MAP3K8 were seen to regulate the molecular switch between leukocyte-cell adhesion to cell-substrate adhesion. SIGNIFICANCE: Our study demonstrated that irradiated endothelium supports leukocyte adhesion and migration but shifts to substrate adhesion dependent cell spreading under radioprotected conditions in order to repair the monolayer damage from the radiation. The genes responsible for the shift were identified and can be employed to manipulate cell adhesion characteristics for the treatment of diseases caused by radiation or inflammation.


Assuntos
Amifostina/farmacologia , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Adesão Celular , Endotélio Vascular/metabolismo , Raios gama , Leucócitos/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos da radiação , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/efeitos da radiação , Protetores contra Radiação/farmacologia
6.
J Renin Angiotensin Aldosterone Syst ; 20(3): 1470320319868890, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31486700

RESUMO

BACKGROUND: The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy. METHOD: The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile. RESULTS: Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients (P=0.02). After statin therapy, low-density lipoprotein cholesterol (P<0.0001), C-reactive protein (P=0.03), von Willebrand factor (P=0.03) and vascular endothelial growth factor (P<0.01) decreased and flow-mediated vasodilation improved (P<0.001). Statins had no significant effect on blood pressure. CONCLUSIONS: Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/fisiopatologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Biomarcadores/sangue , Quimioterapia Combinada , Endotélio Vascular/efeitos dos fármacos , Hipertensão Essencial/sangue , Feminino , Fluvastatina/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Masculino , Pessoa de Meia-Idade , Placebos
7.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480330

RESUMO

BACKGROUND: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease. METHODS AND RESULTS: Elevated blood pressure measured by tail-cuff plethysmography in mice with keratinocyte-specific IL-17A overexpression (K14-IL-17Aind/+ mice) was significantly reduced in response to telmisartan. Importantly, vascular dysfunction, as assessed by isometric tension studies of isolated aortic rings, vascular inflammation measured by flow cytometry analysis of CD45+CD11b+ immune cells, as well as the increased peripheral oxidative stress levels assessed by L-012-enhanced chemiluminescence were not attenuated by telmisartan treatment of K14-IL-17Aind/+ mice, nor was the persisting skin inflammation. CONCLUSION: We provide first evidence for an effective antihypertensive treatment in experimental psoriasis by AT1 blockade, but without any impact on vascular inflammation and dysfunction in our mouse model of severe psoriasis-like skin disease. This suggests that vascular function and inflammation in psoriasis might not be attenuated as long as skin inflammation persists.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Inflamação/patologia , Psoríase/tratamento farmacológico , Psoríase/fisiopatologia , Telmisartan/uso terapêutico , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia , Telmisartan/farmacologia
8.
Anal Bioanal Chem ; 411(27): 7157-7164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31492998

RESUMO

Endothelial damage is a major manifestation in many forms of heart and lung injuries induced by lipopolysaccharide (LPS), but the biochemical responses and activation mechanisms of endothelial cells have not been fully explicit. In this study, the biochemical changes to endothelial cells exposed to LPS were investigated by synchrotron FTIR microspectroscopy at a single-cell level. We found that the whole infrared spectrum of endothelial cells shifted after LPS treatment, indicating chemical component changes within cells. Principal component analysis (PCA) and t tests on subspectra (fatty acid region, protein region, and nucleic acid-sugar region, respectively) further showed that sugar components as well as fatty acids changed dramatically while proteins had no significant variation following LPS exposure. These results suggested that the glycocalyx layer structure on endothelial cell membrane may be mainly influenced by LPS and also proved that synchrotron FTIR microspectroscopy was a useful technique to evaluate the biochemical changes of endothelial damage at the single-cell level. Graphical abstract.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Análise de Célula Única , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Síncrotrons , Endotélio Vascular/citologia , Células Endoteliais da Veia Umbilical Humana , Humanos
9.
Food Chem Toxicol ; 133: 110799, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493463

RESUMO

Aluminum (Al) is toxic for humans and animals. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against cardiovascular changes in rats exposed to both high and low dietary levels of Al. Indeed, EWH has been previously shown to improve cardio metabolic dysfunctions induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment. After Al treatment, rats co-treated with EWH did not show vascular dysfunction or increased blood pressure as was observed in non EWH-cotreated animals. Indeed, co-treatment with EWH prevented the following effects observed in both aorta and mesenteric arteries: the increased vascular responses to phenylephrine (Phe), the decreased ACh-induced relaxation, the reduction on endothelial modulation of vasoconstrictor responses and the nitric oxide bioavailability, as well as the increased reactive oxygen species production from NAD(P)H oxidase. Altogether, our results suggest that EWH could be used as a protective agent against the harmful vascular effects after long term exposure to Al.


Assuntos
Antioxidantes/farmacologia , Proteínas do Ovo/farmacologia , Clara de Ovo/química , Hidrolisados de Proteína/farmacologia , Doenças Vasculares/prevenção & controle , Alumínio , Animais , Antioxidantes/química , Ciclo-Oxigenase 2/metabolismo , Proteínas do Ovo/química , Endotélio Vascular/efeitos dos fármacos , Hidrólise , Masculino , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Tromboxano-A Sintase/metabolismo , Doenças Vasculares/induzido quimicamente , Vasoconstrição/efeitos dos fármacos
10.
Biol Pharm Bull ; 42(9): 1456-1463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474707

RESUMO

α-Lipoic acid (ALA) is used as a dietary supplement and known as an anti-oxidant. The present study aimed to examine whether ALA improves endothelial dysfunction in high-fat diet-fed obese mice. After feeding a high-fat diet to Institute of Cancer Research (ICR) mice for 4 weeks, the mice were maintained with a high-fat diet (group HF) or a high-fat diet containing ALA (25 mg/d, group HF + ALA) for an additional 20 weeks. Age-matched normal diet-fed mice were also used (group Normal). Chronic oral treatment with ALA did not affect various plasma parameters or body weights. As compared with the aortas of Normal mice, those from HF mice showed impaired endothelium-dependent relaxation in response to clonidine. However, such an impairment was not observed in the aortas from HF + ALA mice. The plasma levels of thiobarbituric acid reactive substances, an indicator of oxidative stress, were significantly decreased in HF + ALA mice compared with HF mice, confirming the anti-oxidative effects of ALA. In addition, when the impaired clonidine-induced vasorelaxation of aortas from normal mice under high glucose conditions was used as a model of acute oxidative stress, the vasorelaxation responses were improved in the presence of ALA at 100 µM. Our results suggested that the chronic oral administration of ALA improves endothelial dysfunction in high-fat diet-fed obese mice possibly through the reduction in oxidative stress in vivo.


Assuntos
Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Dieta Hiperlipídica , Endotélio Vascular/efeitos dos fármacos , Obesidade/tratamento farmacológico , Ácido Tióctico/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Aorta/fisiopatologia , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Endotélio Vascular/fisiopatologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos ICR , Obesidade/sangue , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ácido Tióctico/administração & dosagem
11.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370156

RESUMO

Diabetes mellitus is one of the major risk factors for cardiovascular disease and is an important health issue worldwide. Long-term diabetes causes endothelial dysfunction, which in turn leads to diabetic vascular complications. Endothelium-derived nitric oxide is a major vasodilator in large-size vessels, and the hyperpolarization of vascular smooth muscle cells mediated by the endothelium plays a central role in agonist-mediated and flow-mediated vasodilation in resistance-size vessels. Although the mechanisms underlying diabetic vascular complications are multifactorial and complex, impairment of endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells would contribute at least partly to the initiation and progression of microvascular complications of diabetes. In this review, we present the current knowledge about the pathophysiology and underlying mechanisms of impaired EDH in diabetes in animals and humans. We also discuss potential therapeutic approaches aimed at the prevention and restoration of EDH in diabetes.


Assuntos
Fatores Biológicos/genética , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Endotélio Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Canais de Potássio Cálcio-Ativados/genética , Animais , Fatores Biológicos/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Junções Comunicantes/patologia , Regulação da Expressão Gênica , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Potenciais da Membrana/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Canais de Potássio Cálcio-Ativados/metabolismo , Fatores de Risco , Transdução de Sinais , Vasodilatação/efeitos dos fármacos
12.
Kidney Blood Press Res ; 44(4): 835-847, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430746

RESUMO

OBJECTIVES: We aimed to assess whether a 7-day high-salt (HS) diet affects endothelium-dependent and/or endothelium-independent microvascular function in the absence of changes in arterial blood pressure (BP), and to determine whether such microvascular changes are associated with changes in body composition and fluid status in healthy young humans. MATERIALS AND METHODS: Fifty-three young healthy individuals (28 women and 25 men) were assigned to a 7-day low-salt diet (<3.5 g salt/day) followed by a 7-day HS diet (∼14 g salt/day). Skin microvascular blood flow in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed by laser Doppler flowmetry, and BP, heart rate (HR), plasma renin activity (PRA), serum aldosterone, serum and 24 h-urine sodium, potassium, urea and creatinine levels, together with body composition and fluid status measurement with a 4-terminal portable impedance analyzer were measured before and after diet protocols. RESULTS: BP, HR, body composition and fluid status were unchanged, and PRA and serum aldosterone level were significantly suppressed after HS diet. ACh-induced dilation (AChID) was significantly impaired, while SNP-induced dilation was not affected by HS diet. Impaired AChID and increased salt intake, as well as impaired AChID and suppressed renin-angiotensin system were significantly positively correlated. Changes in body composition and fluid status parameters were not associated with impaired AChID. CONCLUSION: 7-day HS diet impairs microvascular reactivity by affecting its endothelium-dependent vasodilation in young healthy individuals. Changes are independent of BP, body composition changes or fluid retention, but are the consequences of the unique effect of HS on endothelial function.


Assuntos
Cloreto de Sódio na Dieta/farmacologia , Vasodilatação/efeitos dos fármacos , Adolescente , Pressão Sanguínea/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Líquidos Corporais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Microcirculação , Microvasos/citologia , Fatores de Tempo , Adulto Jovem
13.
Int J Mol Sci ; 20(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466215

RESUMO

Food peptides contain a very wide range of diversified structures, which explains their diverse range of functional activities. Proatherogenic endothelium is related to vasoconstriction, inflammation, and oxidative stress. In this line, four synthetic bioactive peptides from dry-cured pork ham, previously identified according to their Angiotensin I Converting Enzyme (ACE) inhibitory capacity and high bioavailability, were tested. Among them, KPVAAP displayed an estimated IC50 of 59.22 µM for human ACE inhibition, and docking simulations demonstrated the consistency of the noncompetitive binding with the protein. The addition of synthetic peptides to human endothelial cells significantly prevents the expression of genes related to endothelial dysfunction and inflammation (eNOS, ICAM-1, VCAM-1, IL-6) and lowers NF-κB activation (all p < 0.05). In silico dockings showed that the four bioactive peptides interact with the regulatory subunit NEMO of the NF-κB transcription factor at the same site as other characterized inhibitors (CC2-LZ region). This is the first study linking experimental and computational approaches that shows NF-κB to be the target of biopeptides of food origin. These multifunctional peptides from dry-cured pork ham make them good candidates for further research into their therapeutic or preventive use to attenuate the inflammatory atherosclerotic process.


Assuntos
Anti-Inflamatórios/farmacologia , Células Endoteliais/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Proteínas de Carne/química , Simulação de Acoplamento Molecular , Oligopeptídeos/farmacologia , Anti-Inflamatórios/química , Sítios de Ligação , Linhagem Celular , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Quinase I-kappa B/química , Oligopeptídeos/química , Ligação Proteica
14.
Life Sci ; 233: 116745, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31404524

RESUMO

Hypertension is one of the major risk factors for cardiovascular disease worldwide and is striking more young people, which is characterized by impaired vascular endothelial function. To find the functional lncRNAs associated with hypertension, high throughput lncRNA microarray were used to analyze expression profile of the lncRNAs in the aortic vascular endothelial cells (VECs) of spontaneously hypertensive rats (SHRs). The tail vein injection of siRNA was used to study the influence of lncRNA AK094457 inhibition on endothelial function in vivo. In vitro, endothelial function was studied in endothelial cells transfected with lncRNA AK094457-overexpressed vectors and siRNAs. pPPARγ and iNOS protein levels were detected with Western blot. Elisa assay was used to analyze the secretion of AngII, ET-1, ROS and LDH level. The nitrite/nitrate (NO2-/NO3-) concentration was measured using a colorimetric assay. LncRNA AK094457 was a most upregulated lncRNA in SHRs. It is showed that downregulation of AK094457 significantly reduced rat arterial pressure, increased activation of endothelial PPARγ, and suppressed serum contents of AngII and NO in vivo. Furthermore, results from gain-and-loss of function in primary aortic endothelial cells indicated that AK094457 negatively regulated activation of PPARγ and promoted AngII-mediated endothelial dysfunction, manifested by decreased capacities of cell proliferation and migration, and increased levels of ROS production and LDH release. In conclusion, lncRNA AK094457 is identified as a key regulator in blood pressure and endothelial function, which can increase AngII-induced hypertension and endothelial dysfunction via suppression of PPARγ.


Assuntos
Angiotensina II/toxicidade , Endotélio Vascular/patologia , Hipertensão/patologia , Músculo Liso Vascular/patologia , PPAR gama/antagonistas & inibidores , RNA Longo não Codificante/genética , Vasoconstritores/toxicidade , Animais , Proliferação de Células , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/genética , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Endogâmicos SHR , Transdução de Sinais , Remodelação Vascular
15.
Fitoterapia ; 138: 104299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404616

RESUMO

Gerbera piloselloides (L.) Cass. (Compositae) possesses various biological effects. It is used as an oriental remedy for relieving cough and resolving phlegm. The present study is to investigate the vasodilation effects of Gerbera piloselloides on isolated rat mesenteric arteries (MAs) and the potential mechanism. Different organic extracts of Gerbera piloselloides were tested, and an HPLC-UV-FD-based analytical method was established to identify the active constituents. The principal components, namely, 8-MOP (8-methoxypsoralan) and 8-MSD (8-methoxysmyrindiol), were found to be predominant in the extracts of petroleum ether and dichloroform, which showed stronger vasodilation activities. 8-MSD was isolated from Gerbera piloselloides by silica gel column chromatography coupled with a Waters 2545 high throughput autopurification system, and its vasodilation effects were explored by an assay of tension on rat MA rings. The results suggest that 8-MSD induces vascular relaxation in rat MAs via an endothelium-dependent mechanism involving the Kir channel, which enables Ca2+ entry in the cell and activates production of NO. The present research indicates that 8-MSD may be therapeutically useful as an anti-hypertension agent and to potentially treat cardiovascular and gastrointestinal diseases.


Assuntos
Asteraceae/química , Artérias Mesentéricas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação , Vasodilatadores/farmacologia , Animais , China , Endotélio Vascular/efeitos dos fármacos , Feminino , Técnicas In Vitro , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Vasodilatadores/isolamento & purificação
16.
Phytother Res ; 33(11): 2989-2995, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31423626

RESUMO

Impaired endothelial function is an important risk factor for cardiovascular disease (CVD). Curcumin supplementation might be an appropriate approach to decrease the complications of CVD. Randomized controlled trials assessing the effects of curcumin supplementation on endothelial function were included. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between-study heterogeneities were estimated using the Cochran's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model, and weighted mean differences (WMDs) were considered as the overall effect sizes. Ten studies with 11 effect sizes were included. We found a significant increase in flow-mediated dilation (FMD) following curcumin supplementation (WMD: 1.49; 95% CI [0.16, 2.82]). There was no effect of curcumin supplement on pulse wave velocity (PWV; WMD: -41.59; 95% CI [-86.59, 3.42]), augmentation index (Aix; WMD: 0.71; 95% CI [-1.37, 2.79]), endothelin-1 (ET-1; WMD: -0.30; 95% CI [-0.96, 0.37]), and soluble intercellular adhesion molecule-1 (sICAM-1; WMD: -10.11; 95% CI [-33.67, 13.46]). This meta-analysis demonstrated the beneficial effects of curcumin supplementation on improving FMD, though it did not influence PWV, Aix, Et-1, and sICAM-1.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Curcumina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Idoso , Doenças Cardiovasculares/fisiopatologia , Suplementos Nutricionais , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
17.
J Trauma Acute Care Surg ; 87(3): 614-622, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31454337

RESUMO

BACKGROUND: Extracellular histones are major mediators of organ dysfunction and death in sepsis, and they may cause microcirculatory dysfunction. Heparins have beneficial effects in sepsis and have been reported to bind to histones and neutralize their cytotoxicity. The aim of this study was to investigate the impact of histones on intestinal microcirculation and the intestinal endothelium and to discuss the protective effect of unfractionated heparin (UFH) on the endothelial cytotoxicity and microcirculatory dysfunction induced by histones. METHODS: Anesthetized rats were infused with 30 mg/kg calf thymus histones, and UFH was administered intravenously at a concentration of 100 IU/kg per hour. The intestinal microcirculation was visualized and measured with incident dark field microscope. Plasma von Willebrand factor (vWF) and soluble thrombomodulin were detected, and structural changes in the rat intestinal microvascular endothelium were examined. The effects of histones and UFH on cell survival rates, vWF release and calcium influx were investigated in human intestinal microvascular endothelial cells (HIMECs). RESULTS: Histone infusion caused severe intestinal microcirculatory dysfunction in the absence of obvious hemodynamic changes, and UFH protected intestinal microcirculation in histone-infused rats. Concentrations of the plasma endothelial injury markers vWF and soluble thrombomodulin were elevated, and structural abnormalities were found in the intestinal microvascular endothelium in the histone-infused rats. These events were attenuated by UFH. In vitro, UFH significantly reduced the histone-induced cytotoxicity of HIMECs, reduced the release of vWF from the cytoplasm into the culture medium, and inhibited calcium influx into HIMECs. CONCLUSION: Histones induce intestinal microcirculatory dysfunction followed by direct injury to the endothelial cells; UFH protects the intestinal microcirculation partly by antagonizing the endothelial toxicity of histones.


Assuntos
Heparina/farmacologia , Histonas/toxicidade , Intestinos/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/ultraestrutura , Humanos , Técnicas In Vitro , Intestinos/efeitos dos fármacos , Masculino , Microscopia Eletrônica , Ratos , Ratos Wistar
18.
Adv Exp Med Biol ; 1155: 407-414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468418

RESUMO

High-intensity resistance exercise has been shown to increase arterial stiffness and reduce vascular endothelial function. Taurine supplementation has a favorable effect on maintaining vascular function. We had previously reported that taurine supplementation attenuated increases in resistance exercise-induced arterial stiffness. In the present study, we further investigate the effects of taurine supplementation on vascular endothelial function at rest and after resistance exercise.Twenty-nine healthy men were recruited and randomly assigned to either the placebo supplement group (n = 14) or the taurine supplement group (n = 15) in a double-blinded manner. Subjects were required to ingest 6 g of either a placebo or the taurine supplement for 2 weeks prior to and 3 days following the exercise. Two weeks after the commencement of supplementation, the subjects were asked to perform 2 sets of 20 repetitive unilateral maximal-effort resistance exercise of the elbow flexors on a Biodex isokinetic dynamometer, with each contraction lasting 3 s, with 1 repetition performed every 9 s and 4 min rest in between sets. We evaluated the changes in brachial artery flow-mediated dilation (FMD) in the non-exercised arm as an index of vascular endothelial function. Relative and absolute FMDs were measured prior to supplementation, before exercise, and 24, 48, and 96 h after exercise.Two weeks of taurine supplementation significantly increased both relative and absolute FMDs. Baseline diameter significantly increased at 96 h following the exercise in both groups. However, there was no change in the peak diameter. Consequently, both relative and absolute FMDs were significantly reduced at 96 h after the exercise in both groups. Taurine supplementation does not affect resistance exercise-induced reduction in FMD.Two weeks of taurine supplementation (6 g/day) significantly increased vascular endothelial function at rest; however, taurine supplementation did not improve resistance exercise-induced reduction in FMD.


Assuntos
Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Treinamento de Resistência , Taurina/farmacologia , Vasodilatação , Artéria Braquial , Endotélio Vascular/fisiologia , Humanos , Masculino
19.
Biosci Biotechnol Biochem ; 83(11): 1992-1999, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31362597

RESUMO

The present study focused on the effect of paeonol, one of the main components of Guizhi Fuling Pill, on blood pressure, cerebral blood flow, and vascular endothelium injury in spontaneously hypertensive rats to provide theoretical basis for the treatment of hypertension. After treatment with paeonol, the mean arterial pressure (MAP) of LSHRT and HSHRT rats decreased gradually with the prolongation of treatment time. The systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd) and mean blood flow velocity (Vm) were significantly increased after paeonol treatment (p < 0.05). Paeonol effectively improved the blood pressure and increased the cerebral blood flow velocity in spontaneously hypertensive rats. This may be related to the fact that paeonol reduced the blood viscosity and the oxidative stress and improved the antioxidant capacity. Moreover, paeonol protected vascular endothelial cells and reduced vascular endothelial injury in spontaneously hypertensive rats.


Assuntos
Acetofenonas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Hipertensão/prevenção & controle , Animais , Pressão Sanguínea/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Hemorreologia/efeitos dos fármacos , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , NADPH Oxidase 4/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Molécula 1 de Adesão de Célula Vascular/metabolismo
20.
Molecules ; 24(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362388

RESUMO

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 µM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 µM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 µM BaCl2 (Kir), 10 µM glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p < 0.05) reduced the ARI-induced relaxation. ARI significantly (p < 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/química , Canais de Potássio/química , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Cloratos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Estrutura Molecular , Óxido Nítrico/metabolismo , Fenilefrina/farmacologia , Canais de Potássio/agonistas , Prostaglandinas/farmacologia , Ratos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/química , Vasodilatadores/farmacologia
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