Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.524
Filtrar
1.
Life Sci ; 236: 116865, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525428

RESUMO

AIMS: Endothelial dysfunction is one of the earliest symptoms in septic patients and plays an important role in the cardiovascular alterations. However, the endothelial mechanisms involved in the impaired sympathetic regulation of the cardiovascular system are not clear. This study aimed to determine the role of the endocardial endothelium (EE) in the cardiac ß-adrenergic (ß-AR) remodeling at the early phase of endotoxemic shock. MAIN METHODS: Rats received either lipopolysaccharide (LPS) or saline (control) intravenously. Three hours later, ß-AR cardiac contractility was evaluated on papillary muscles with or without a functional EE. KEY FINDINGS: Isoproterenol-induced contractility was strongly increased in papillary muscles from LPS rats. A similar increase was observed with a ß1-AR stimulation, whereas ß2-AR and ß3-AR produced similar contractility in control and LPS treatments. The removal of the EE did not modify ß1-AR-induced contractility in controls, whereas it abolished the increased ß1-AR response in LPS-treated muscles. In LPS-treated papillary muscle, the increased ß1-AR-induced contractility was not modified by pretreatment with a NOS inhibitor or an endothelin receptor antagonist. Conversely, the increased ß1-AR-induced contractility was abolished by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, as well as by selective inhibitors of COX1 and COX2. An early treatment with indomethacin improved the survival of LPS rat. SIGNIFICANCE: Our results suggest that the EE is involved in the increased cardiac ß1-AR contractility in the early phase of endotoxemic shock. This effect is mediated through the activation of COX1 and COX2 and suggests these may be novel putative therapeutic targets during endotoxemic shock.


Assuntos
Ciclo-Oxigenase 1/metabolismo , Endotélio Vascular/fisiopatologia , Endotoxemia/fisiopatologia , Proteínas de Membrana/metabolismo , Contração Miocárdica , Músculos Papilares/fisiopatologia , Receptores Adrenérgicos beta 1/metabolismo , Animais , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
2.
Neuron ; 103(3): 367-379, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394062

RESUMO

Traumatic brain injury (TBI) is one the most common human afflictions, contributing to long-term disability in survivors. Emerging data indicate that functional improvement or deterioration can occur years after TBI. In this regard, TBI is recognized as risk factor for late-life neurodegenerative disorders. TBI encompasses a heterogeneous disease process in which diverse injury subtypes and multiple molecular mechanisms overlap. To develop precision medicine approaches where specific pathobiological processes are targeted by mechanistically appropriate therapies, techniques to identify and measure these subtypes are needed. Traumatic microvascular injury is a common but relatively understudied TBI endophenotype. In this review, we describe evidence of microvascular dysfunction in human and animal TBI, explore the role of vascular dysfunction in neurodegenerative disease, and discuss potential opportunities for vascular-directed therapies in ameliorating TBI-related neurodegeneration. We discuss the therapeutic potential of vascular-directed therapies in TBI and the use and limitations of preclinical models to explore these therapies.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Circulação Cerebrovascular , Microvasos/patologia , Doenças Neurodegenerativas/etiologia , Acoplamento Neurovascular , Animais , Barreira Hematoencefálica , Lesões Encefálicas Traumáticas/fisiopatologia , Isquemia Encefálica/etiologia , Progressão da Doença , Endotélio Vascular/fisiopatologia , Humanos , Microcirculação , Micronutrientes/farmacocinética , Modelos Animais , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/prevenção & controle , Neuroimagem
3.
Int Heart J ; 60(4): 854-861, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31257335

RESUMO

The aim of this single-arm pilot study was to determine the effects of whole-body vibration training (WBVT) on endothelial function in elderly patients with cardiovascular diseases, as well as its safety. A total of 20 elderly patients with stable cardiovascular diseases underwent WBVT, which consisted of five static resistance training exercises (squats, wide stance squats, toe-stands, squats + band, and front lunges). The parameters of WBVT included vertical vibrations, 30 Hz frequency, and a 3-mm peak-to-peak amplitude. Each vibration session lasted 30 seconds, with 120 seconds of rest between sessions. Before and after WBVT, the reactive hyperemia peripheral arterial tonometry index (RH-PAT index) and transcutaneous oxygen pressure (tcPO2) were recorded as a measure of endothelial function and peripheral blood circulation. Systolic blood pressure, diastolic blood pressure, heart rate, and arterial oxygen saturation of pulse oximetry (SpO2) were measured at each rest interval as well as before and after WBVT. All patients completed our WBVT protocol without adverse events. The RH-PAT index significantly increased following WBVT (1.42 to 2.06, P < 0.001). There were no significant changes in heart rate (P = 0.777), systolic blood pressure (P = 0.183), diastolic blood pressure (P = 0.925), or SpO2 (P = 0.248) during WBVT. In conclusion, we demonstrated the acute effects of WBVT on endothelial function, with no reports of adverse events. These findings support the need for further randomized controlled studies to investigate the long-term effects of WBVT.


Assuntos
Artérias/fisiopatologia , Doenças Cardiovasculares/terapia , Endotélio Vascular/fisiopatologia , Modalidades de Fisioterapia/instrumentação , Vasodilatação/fisiologia , Idoso , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Força Muscular/fisiologia , Projetos Piloto , Pletismografia , Estudos Retrospectivos , Resultado do Tratamento , Vibração
4.
Isr Med Assoc J ; 21(6): 408-411, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31280511

RESUMO

BACKGROUND: Erectile dysfunction (ED) is a syndrome associated with endothelial dysfunction, which may predict cardiovascular events in men presenting with this syndrome. It has been shown to be associated with a higher rate of acute myocardial infarction and cardiovascular mortality, vascular inflammation, and impaired endothelial function. In this review we present the literature findings and describe the mechanistic pathways that are known to be involved in this syndrome and its related clinical consequences.


Assuntos
Doenças Cardiovasculares/complicações , Endotélio Vascular/fisiopatologia , Disfunção Erétil/complicações , Transtornos do Sono-Vigília/complicações , Adulto , Animais , Doenças Cardiovasculares/fisiopatologia , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Transtornos do Sono-Vigília/fisiopatologia
5.
High Blood Press Cardiovasc Prev ; 26(4): 305-319, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264084

RESUMO

INTRODUCTION: There are current trials investigating the effect of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome (MetS); however, the findings are controversial. AIM: This systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to summarize the effects of resveratrol supplementation on endothelial activation and blood pressures among patients with MetS and related disorders. METHODS: We searched systematically online databases including: PubMed-Medline, Embase, ISI Web of Science and Cochrane Central Register of Controlled Trials until October, 2018. Two independent authors extracted data and assessed the quality of included articles. Data were pooled using the fixed- or random-effects model and considered as standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Out of 831 electronic citations, 28 RCTs (with 33 findings reported) were included in the meta-analyses. The findings showed that resveratrol intervention significantly increased flow-mediated dilatation (FMD) levels (SMD 1.77; 95% CI 0.25, 3.29; P = 0.02; I2: 96.5). However, resveratrol supplements did not affect systolic blood pressure (SBP) (SMD - 0.27; 95% CI - 0.57, 0.03; P = 0.07; I2: 88.9) and diastolic blood pressure (DBP) (SMD - 0.21; 95% CI - 0.52, 0.11; P = 0.19; I2: 89.8). CONCLUSIONS: Resveratrol supplementation significantly increased FMD among patients with MetS and related disorders, but did not affect SBP and DBP. Additional prospective studies are needed to investigate the effect of resveratrol supplementation on endothelial function and blood pressures, using higher-dose of resveratrol with longer durations.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Resveratrol/uso terapêutico , Vasodilatação/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Adulto , Idoso , Suplementos Nutricionais/efeitos adversos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Resveratrol/efeitos adversos , Resultado do Tratamento , Vasodilatadores/efeitos adversos
6.
Croat Med J ; 60(3): 265-272, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31187955

RESUMO

AIM: To assess the effect of air, gas mixture composed of 50% nitrogen and 50% oxygen (nitrox 50), or gas mixture composed of 1% nitrogen and 99% oxygen (nitrox 99) on bubble formation and vascular/endothelial function during decompression after self-contained underwater breathing apparatus diving. METHODS: This randomized controlled study, conducted in 2014, involved ten divers. Each diver performed three dives in a randomized protocol using three gases: air, nitrox 50, or nitrox 99 during ascent. The dives were performed on three different days limited to 45 m sea water (msw) depth with 20 min bottom time. Nitrogen bubbles formation was assessed by ultrasound detection after dive. Arterial/endothelial function was evaluated by brachial artery flow mediated dilatation (FMD) before and after dive. RESULTS: Nitrox 99 significantly reduced bubble formation after cough compared with air and nitrox 50 (grade 1 vs 3 and vs 3, respectively, P=0.026). Nitrox 50 significantly decreased post-dive FMD compared with pre-dive FMD (3.62 ± 5.57% vs 12.11 ± 6.82% P=0.010), while nitrox 99 did not cause any significant change. CONCLUSION: Nitrox 99 reduced bubble formation, did not change post-dive FMD, and decreased total dive duration, indicating that it might better preserve endothelial function compared with air and nitrox 50 dive protocols.


Assuntos
Doença da Descompressão/prevenção & controle , Descompressão/métodos , Mergulho/fisiologia , Endotélio Vascular/fisiopatologia , Nitrogênio/uso terapêutico , Oxigênio/uso terapêutico , Adulto , Ar , Artéria Braquial/fisiopatologia , Doença da Descompressão/diagnóstico por imagem , Doença da Descompressão/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrogênio/química , Oxigênio/química , Ultrassonografia , Vasodilatação
7.
Sheng Li Xue Bao ; 71(3): 485-490, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31218340

RESUMO

The incidence and mortality rates of diabetes with cardiovascular complications are continually rising, and diabetic cardiovascular disease is becoming a major public health issue that threatens human health. Acute endothelial dysfunction and chronic cellular damage caused by diabetes are important risk factors for diabetic cardiovascular disease and related mortality. Adiponectin is an adipocyte-derived molecule with significant cytoprotective effects, including the protection against diabetes-induced vascular endothelial injury. Here we review the mechanisms of adiponectin protective effects on acute vascular endothelial dysfunction and chronic structural damage induced by diabetes.


Assuntos
Adiponectina/fisiologia , Doenças Cardiovasculares/complicações , Diabetes Mellitus/patologia , Endotélio Vascular/fisiopatologia , Humanos
8.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(3. Vyp. 2): 68-75, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184627

RESUMO

To study the relationship between cerebral perfusion with arterial hypertension (AH) and the state of endothelium in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Seventy-eight patients with RA were divided into two groups: with- and without AH.The functional methods included ultrasonic duplex angioscanning and dopplerografy of the extracranial and intracranial arteries of the head and neck and daily 24 hour monitoring of arterial blood pressure (BP). C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), von Willebrand Factor antigen (vWF AG), interleukin-8 (Il-8), rheumatoid factor (RF) IgG, endothelin-1 (ET-1) were determined by immunoenzyme analysis and velocity of sedimentation (VS). The dysfunction of endothelium was evaluated by calculation of the number of desquamated endotheliocytes cells (DE). RESULTS: AH occurred in 46 (59%) patients. Cerebral hypoperfusion was observed in patients with RA in whom the reduction in the high-speed indices of blood flow were correlated with BP increase. There were negative correlations between the linear speed of blood flow on the common carotid arteries and average day and night systolic BP, average day and night diastolic BP, indices of time systolic BP and diastolic BP and avariability of BP. The same results were established for the intracranial arteries: inverse correlations between the linear speed on the anterior cerebral arteries and average day systolic BP. The signs of endothelial dysfunction represented by significant differences among the indices of activation of endothelium in RA patients in comparison with the control group were shown. Content of ET-1, sVCAM-1, vWF AG, Il-8, CRP was higher in RA. The number of DE was significantly higher as well. These indices showed significant differences depending on RA activity. Correlation analysis revealed that the markers of endothelium activation sVCAM-1, vWF AG were positively correlated with the indices of immune inflammation. CONCLUSION: An increase in the activity of inflammatory process in RA leads to endothelial dysfunction, which contributes to the increase in the peripheral vascular resistance of cerebral arteries, reduction in the high-speed indices of blood flow, growth of BP variability and the increase in load by pressure.


Assuntos
Artrite Reumatoide , Circulação Cerebrovascular , Hipertensão , Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Biomarcadores , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/complicações , Molécula 1 de Adesão de Célula Vascular
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 210-214, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106541

RESUMO

OBJECTIVE: To determine the effects of aging on endothelium-dependent vasodilation of human artery. METHODS: Vessel tension changes induced by acetylcholine (ACh) and endothelial-derived hyperpolarizing factor (EDHF) on gastroepiploic artery rings were recorded in 15 patients with stomach cancer aged between 51 and 83 years. The mRNA expressions of endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX), cystathionineγ lyase (CSE) and the C-type natriuretic peptide (CNP) in the artery vessels were detected by qRT-PCR. RESULTS: Both endothelium-dependent and EDHF induced vasodilation decreased with age (P<0.05). The mRNA expressions of eNOS, CSE and CNP also decreased with age (P<0.05), except COX. CONCLUSION: Aging could impair the function of endothelium-dependent vasodilation and EDHF-induced vasodialtion of human artery, possibly due to decreased NO, H2S and CNP in artery.


Assuntos
Fatores Etários , Artérias/fisiopatologia , Endotélio Vascular/fisiopatologia , Vasodilatação , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Óxido Nítrico , Neoplasias Gástricas/patologia
10.
Wiad Lek ; 72(4): 523-526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055525

RESUMO

OBJECTIVE: Introduction: The study increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine and in the world necessitates the research into mechanisms of mutual burden and the search for new factors in the pathogenesis of this comorbidity progression . The aim: To establish the role of endothelial dysfunction in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 135 patients were examined: of which 52 patients with non-alcoholic steatohepatitis with obesity I degree (1 group), 53 patients with nonalcoholic steatohepatitis with comorbid obesity of the I degree and chronic kidney disease of the І-ІІ stage (group 2). The control group consisted of 30 practically healthy persons of the corresponding age and sex. The average age of patients was (45.8 ± 3.81) years. RESULTS: Results: The results of the study showed that in patients with NASH, a significant increase in the content of NO in the blood was detected in comparison with the index in PHP (p <0,05) in group 1 - in 2,1 times, in the 2nd group - in 2,6 times (p <0,05). The role of nitrosative stress in the pathogenesis of NASH was proved, the confirmation of which is the increase in the concentration of nitrosothiols, peroxynitrite and other metabolites NO in the blood. Increased peroxynitrite formation due to the generation of NO by leukocytes is an important aspect of the damaging effect and inflammation process in NASH. Pathological hyperproduction of NO by endothelial cells and leukocytes from inflammatory infiltrates in the liver contributes to the development of nitrosative stress in NASH. The established hypernitrate in blood may also be considered compensatory in response to hyperproduction of ET-1 in all observational groups. CONCLUSION: Conclusions: Confirmation of the presence of endothelial dysfunction (ED) in patients with NASH with CKD resulted in a probable growth of the number of desquamated endothelial cells (DEC) in the 2nd group of patients in 1.9 times (p2 <0.05). Generation by neutrophils during the exacerbation of NASH of a significant number of active forms of oxygen and nitrogen and hyperproduction of endothelial cells and endometrial lymphocytes with progressive damage to the endothelium (growth of DEC) leads to significant ED, accompanied by mosaic angiospasm of the arteries due to hyperproduction of ET-1 and parectic vasodilatation of the veins of the portal vein system because of the hyperproduction of NO.


Assuntos
Endotélio Vascular/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Adulto , Estudos de Casos e Controles , Progressão da Doença , Endotelina-1/metabolismo , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Ucrânia
11.
Angiology ; 70(8): 719-725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31137942

RESUMO

The effects of nicotine replacement therapy (NRT)-aided smoking cessation on vascular function are not fully clarified. We investigated 100 healthy smokers who were motivated to quit and received NRT for a 3-month period. Vascular endothelial function (measured by reactive hyperemia-peripheral arterial tonometry [RH-PAT]), arterial stiffness (measured by augmentation index [AI] and brachial-ankle pulse wave velocity [baPWV]), and systemic inflammation markers (including serum soluble intercellular adhesion molecule-1 [sICAM-1] and interleukin-1ß [IL-1ß]) were assessed at baseline and 3 and 12 months of follow-up. After 3 months of intervention, endothelial function, arterial stiffness, and inflammatory markers significantly improved (RH-PAT increased, AI and baPWV decreased, sICAM-1 and IL-1ß decreased, all P < .05) for the participants who abstained from smoking completely, but for those who did not abstained completely, RH-PAT, AI, baPWV, and IL-1ß remained unchanged. At 12 months follow-up, endothelial function (RH-PAT), arterial stiffness (AI and baPWV), and inflammatory markers (sICAM-1 and IL-1ß) were further improved in participants who abstained from smoking (P < .001), while the above parameters deteriorated in continued smokers (P < .05). In conclusion, vascular dysfunction can be reversible after NRT-aided smoking cessation in healthy smokers and vascular function could be further damaged if they continue smoking.


Assuntos
Hiperemia/tratamento farmacológico , Inflamação/tratamento farmacológico , Abandono do Hábito de Fumar , Dispositivos para o Abandono do Uso de Tabaco , Rigidez Vascular/fisiologia , Adolescente , Adulto , Idoso , Artérias/efeitos dos fármacos , Artérias/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hiperemia/fisiopatologia , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fumantes , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Adulto Jovem
12.
Gene ; 709: 1-7, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31108165

RESUMO

Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. A sustained high glucose environment results in inflammation and endothelial cell dysfunction. However, the underlying mechanisms are still not entirely clear. Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in diverse biological processes, including DM. Previous studies have found that hsa_circ_0068087 is increased in DM patients. In order to identify whether hsa_circ_0068087 plays a role in high glucose (HG)-induced inflammation and endothelial cell dysfunction Human Umbilical Vein Endothelial Cell (HUVECs), quantitative reverse transcription PCR (qRTPCR), tube formation assay, enzyme-linked immunosorbent assay (ELISA) and bifluorescein reporter experiments were employed in this study. The results showed that the expression of hsa_circ_0068087 was upregulated in HUVECs following increases in glucose. Knockdown of hsa_circ_0068087 suppressed HG-induced HUVEC dysfunction and inflammation by suppression of the TLR4/NF-κB/NLRP3 inflammasome signaling pathway. Downregulation of miR-197 reversed hsa_circ_0068087 silence-induced HUVEC dysfunction and inflammation in the HG condition. It was found that TLR4 was the target of miR-197 and that overexpression of TLR4 ameliorated miR-197-induced HUVEC dysfunction and inhibited inflammation in the HG condition. Bifluorescein report experiments confirmed that miR-197 is a potential target of hsa_circ_0068087 and that TLR4 is a potential miR-197 target. Taken together, these results suggest that downregulation of hsa_circ_0068087 ameliorates TLR4/NF-κB/NLRP3 inflammasome-mediated inflammation and endothelial cell dysfunction in the high glucose condition by sponging miR-197.


Assuntos
Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamassomos/fisiologia , Inflamação/genética , MicroRNAs/metabolismo , RNA/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Técnicas de Silenciamento de Genes , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/metabolismo , MicroRNAs/efeitos dos fármacos , MicroRNAs/genética , RNA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
13.
Ter Arkh ; 91(3): 22-26, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-31094454

RESUMO

AIM: The aim of this study was to evaluate the state of the vascular wall in patients with chronic obstructive pulmonary disease (COPD) combined with chronic coronary artery disease (CAD). MATERIALS AND METHODS: The study included 108 patients: 37 patients with COPD and CAD and 71 patients with COPD without CAD. Endothelial function was studied in tests with reactive hyperemia and nitroglycerin. The number of blood plasma desquamated endotheliocytes were determined by the Hladovec method. In patients with COPD identified are signs of vascular wall remodeling: thickening wall of the brachial artery, reduction of the flow-mediated vasodilation. Patients with COPD in combination with CHD demonstrated higher impairments of the vasoregulatory dysfunction of endothelial of the vascular wall. CONCLUSION: In patients with COPD combined with chronic coronary heart disease more pronounced endothelial dysfunction with disturbance of endothelium-dependent vasomotor reactions.


Assuntos
Doença da Artéria Coronariana , Endotélio Vascular , Doença Pulmonar Obstrutiva Crônica , Artéria Braquial , Doença da Artéria Coronariana/fisiopatologia , Endotélio Vascular/fisiopatologia , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Vasodilatação
14.
Intern Med ; 58(10): 1383-1390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31092771

RESUMO

Objective Type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA) are both complicated by arteriosclerosis, resulting in increased rates of cardiovascular events. No previous studies have compared the index between RA and T2DM. We assessed the vascular endothelial function in early-stage arteriosclerosis for each disease to determine the influential factors and compared the extent to which these two diseases cause vascular endothelial dysfunction. Methods This study is a retrospective study based on medical records. Differences in the reactive hyperemia index (RHI) among the groups and factors affecting the RHI in each group was analyzed. The vascular endothelial function was assessed by measuring the RHI using peripheral arterial tonometry. Patients The study subjects were 114 patients with non-functional thyroid tumors (healthy n=14), T2DM (T2DM n=64), and RA (RA n=36). Results The RHI was 2.29 in the control, 1.85 in the T2DM, and 1.83 in the RA group, with values lower in the T2DM and RA groups than in the control group (p=0.033) but not markedly different between the two disease groups. The RHI distribution (<1.68/1.68 to <2.10/≥2.1) was as follows: control group: 14.3%/28.6%/57.1%; T2DM group: 42.2%/39.1%/18.8%; and RA group: 36.1%/44.4%/19.4% (p=0.031), respectively. A multivariate analysis identified the triglyceride level and dyslipidemia in the control group and the Disease Activity Score in 28 joints with the erythrocyte sedimentation rate and fasting plasma glucose level in the RA group to influence the RHI. Conclusion The vascular endothelial function was impaired in approximately 80% of patients with T2DM and RA, with comparable degrees of impairment between the two diseases. No factors affecting the function were identified in the T2DM group, while the function was more impaired in patients with a higher disease activity in the RA group.


Assuntos
Arteriosclerose/fisiopatologia , Artrite Reumatoide/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Hiperemia/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
Nat Commun ; 10(1): 2126, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073164

RESUMO

Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental transcription factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate that the native endothelium itself serves as the primary source of endothelial cells repopulating the vessel wall following injury. We identify Sox17 as a key regulator of endothelial cell regeneration using endothelial-specific deletion and overexpression of Sox17. Endotoxemia upregulates Hypoxia inducible factor 1α, which in turn transcriptionally activates Sox17 expression. We observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. We conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis.


Assuntos
Ciclina E/genética , Endotélio Vascular/fisiopatologia , Endotoxemia/patologia , Proteínas HMGB/metabolismo , Proteínas Oncogênicas/genética , Regeneração/imunologia , Fatores de Transcrição SOXF/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Ciclina E/metabolismo , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Endotoxemia/imunologia , Células HEK293 , Proteínas HMGB/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Oncogênicas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição SOXF/genética , Transdução de Sinais/fisiologia , Regulação para Cima
16.
Scand J Med Sci Sports ; 29(8): 1115-1120, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30968965

RESUMO

Resistance exercise impairs endothelial function. Therefore, it is of paramount importance to devise an effective strategy for restoring endothelial function after resistance exercise. Herein, we tested the hypothesis that resistance exercise-induced endothelial dysfunction would be restored by low-to-moderate intensity cycling. Seventeen young healthy subjects completed two randomized experimental trials: (a) resistance exercise only trial; and (b) cycling after the resistance exercise trial. Following baseline brachial artery flow-mediated dilation (FMD), subjects performed the resistance exercise. Following the resistance exercise, they were asked to rest in the supine position for the assessments of FMD. Subjects in the resistance exercise only trial maintained this supine position for 60 minutes, whereas those in the other trial cycled for 10 minutes after the resistance exercise trial. Subjects were again asked to rest in the supine position after cycling. Then FMD were repeated at 30 and 60 minutes after the resistance exercise in both trials. In the resistance exercise only trial, the increased blood flow and shear rate were disappeared after 1 hour of resting in the supine position, but were maintained in those in the cycling after the resistance trial due to subsequent cycling. Both trials caused a significant impairment in FMD at 10 minutes after the resistance exercise (P < 0.05). This decline was sustained for 60 minutes in the resistance exercise only trial. However, the impaired FMD was restored in the cycling after the resistance exercise trial. In conclusion, impaired endothelial function after the resistance exercise can be restored with 10 minutes of low-to-moderate intensity cycling.


Assuntos
Ciclismo/fisiologia , Artéria Braquial/fisiologia , Endotélio Vascular/fisiopatologia , Fluxo Sanguíneo Regional , Treinamento de Resistência , Humanos , Masculino , Decúbito Dorsal , Adulto Jovem
17.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987118

RESUMO

Physical inactivity and sedentary lifestyle contribute to the widespread epidemic of obesity among both adults and children leading to rising cases of diabetes. Cardiovascular disease complications associated with obesity and diabetes are closely linked to insulin resistance and its complex implications on vascular cells particularly endothelial cells. Endoplasmic reticulum (ER) stress is activated following disruption in post-translational protein folding and maturation within the ER in metabolic conditions characterized by heavy demand on protein synthesis, such as obesity and diabetes. ER stress has gained much interest as a key bridging and converging molecular link between insulin resistance, oxidative stress, and endothelial cell dysfunction and, hence, represents an interesting drug target for diabetes and its cardiovascular complications. We reviewed here the role of ER stress in endothelial cell dysfunction, the primary step in the onset of atherosclerosis and cardiovascular disease. We specifically focused on the contribution of oxidative stress, insulin resistance, endothelial cell death, and cellular inflammation caused by ER stress in endothelial cell dysfunction and the process of atherogenesis.


Assuntos
Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Estresse do Retículo Endoplasmático , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Animais , Humanos , Modelos Biológicos , Resposta a Proteínas não Dobradas
18.
Angiology ; 70(9): 797-801, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30969784

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.


Assuntos
Biomarcadores/sangue , Endotélio Vascular/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Síndrome do Ovário Policístico/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Doenças Vasculares/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangue
19.
Biomed Pharmacother ; 112: 108722, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970521

RESUMO

Microvascular and macrovascular complications are major causes of disability and death in diabetic patients. High levels of blood glucose sabotage the integrity of blood vessels and induce endothelial dysfunction. Fenofibrate is an agonist of peroxisome proliferator-activated receptor α and can reduce the incidence of cardiovascular events in diabetic patients. This study tested the hypothesis that fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction via activating endothelial nitric oxide synthase (eNOS) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A streptozotocin (STZ)-induced diabetic model was established by intraperitoneal injection of STZ (dissolved in sodium citrate buffer) at a dose of 60 mg/kg for 5 consecutive days. Mice were administered fenofibrate (100 mg/kg/d, i.g.) for 14 days. The endothelial function of extracted mouse aortae was examined by evaluating acetylcholine induced endothelium-dependent relaxation combined with phenylephrine-induced vasoconstriction and sodium nitroprusside-induced endothelium-independent relaxation. Superoxide onion (O2-) was determined using dihydroethidium staining of aortae. Functions of mouse aortic endothelial cells (MAECs) were assessed, and expression levels of eNOS and AMPK were determined by Western blotting. Fenofibrate ameliorated the impaired endothelium-dependent relaxation in diabetic mice and decreased the level of intracellular O2- in diabetic mouse aortae. In-vitro, fenofibrate treatment improved the impaired function of MAECs, increased nitric oxide production, and decreased the O2- level, as well as activated eNOS and AMPK phosphorylation in cultured MAECs by high glucose. Fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction, which was possibly related to the activation of eNOS and AMPK phosphorylation.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Fenofibrato/uso terapêutico , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/fisiopatologia , Fenofibrato/farmacologia , Glucose/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , PPAR alfa/agonistas , Estreptozocina
20.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 119-124, 2019 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-30942165

RESUMO

To investigate the effect of piperazine ferulate (PF) on hypertension and endothelial function, and to assess the possible underlying mechanism. Human umbilical vein endothelial cells (HUVEC), adult male Wistar Kyoto (WKY) rats aged 12 to 14 weeks, and spontaneously hypertensive (SH) and Sprague Dawley (SD) rats were used for this study. Cell viability, activities of angiotensin-converting enzyme (ACE) and heme oxygenase-1 (HO-1), in vivo NO synthesis, arterial systolic blood pressure, vascular function, expressions of endothelial NO synthase (eNOS) and phosphorylated-eNOS (p-eNOS) were determined or assessed as appropriate. The results of MTT assay showed the number of viable cells were significantly increased with increase in PF concentration (p < 0.05). The level of expression of ACE was significantly reduced with increase in PF concentration (p < 0.05), while the level of HO-1 expression significantly increased (p < 0.05). Results of DAF-FM fluorescent staining showed that the amounts of NO synthesized in vivo was significantly higher in aortic rings of SH and SD rats treated with PF than in the corresponding control groups (p < 0.05). Treatment with PF in vivo significantly improved impaired acetylcholine-induced aortic relaxation in SH rats. Total eNOS expression was significantly increased after treatment with PF (p < 0.05). The expressions of total eNOS and p-eNOS in both groups were not affected by PF when compared to the control group. These results indicate that PF exerts antihypertensive effect and improves endothelial function in vitro and in vivo via the activation of eNOS.


Assuntos
Anti-Hipertensivos/farmacologia , Endotélio Vascular/enzimologia , Endotélio Vascular/fisiopatologia , Óxido Nítrico Sintase Tipo III/metabolismo , Piperazina/farmacologia , Animais , Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Heme Oxigenase-1/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Óxido Nítrico/metabolismo , Peptidil Dipeptidase A/metabolismo , Fosforilação , Piperazina/química , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Sístole/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA