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OBJECTIVE: Breast cancer is among the highest causes of morbidity and mortality in women. Trastuzumab therapy, which is known to be significantly cardiotoxic, is mainly used to treat patients with resistant breast cancer, including estrogen receptor-positive type. We aimed to show the effects of trastuzumab therapy on endothelial functions of breast cancer patients. METHODS: In this study, a total of 26 participants (24 female and 2 male patients, minimum age: 38 years, maximum age: 79 years, and mean age 57.3±12.7 years) were enrolled in the study. For the statistical evaluation of data, we classified the participants of the study as follows: Pretreatment: Before trastuzumab therapy; Treatment Period 1: 1 month after the first dose of trastuzumab; Treatment Period 2: 4 months after the first dose of trastuzumab; Treatment Period 3: 12 months after the first dose of trastuzumab. We conducted repeated-measures analysis of variance (Greenhouse-Geisser) and paired-sample t-tests to statistically compare the groups using flow-mediated dilation measurements. RESULTS: We determined that there are statistically significant differences between flow-mediated hyperemia and ratio values (flow-mediated dilation) of the groups (p<0.009 and p<0.001, respectively). CONCLUSION: Our data indicate that trastuzumab therapy could have negative effects on endothelial functions in breast cancer patients.
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Antineoplásicos Inmunológicos , Neoplasias de la Mama , Endotelio Vascular , Trastuzumab , Humanos , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , Trastuzumab/administración & dosificación , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Masculino , Adulto , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Factores de Tiempo , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Cerebral blood flow dynamics can be explored through analysis of endothelial frequencies. Our hypothesis posits a disparity in endothelial activity among neonates with perinatal asphyxia, stratified by the presence or absence of neuronal lesions. METHODS: We conducted a retrospective longitudinal study involving newborns treated with hypothermia for moderate to severe asphyxia. Participants were grouped based on the presence or absence of neuronal damage to investigate temporal endothelial involvement in cerebral blood flow regulation. Regional cerebral oxygen saturation (rScO2) was measured using near-infrared spectroscopy (NIRS), and temporal series were analyzed in the frequency domain, utilizing the original frequency of the INVOS™ device. RESULTS: The study included 88 patients, with 53% (47/88) being male and 33% (29/88) demonstrating brain lesions on magnetic resonance imaging. Among them, 86% (76/88) had a gestational age exceeding 37 weeks according to the Ballard scale, and 81% (71/88) had a birth weight exceeding 2500 g. Cohen's d effect size was calculated to assess differences in endothelial frequency between groups, indicating a small effect size based on cerebral MRI findings (Cohen's d values for Day 2 = 0.2351 and Day 3 = 0.2325). CONCLUSION: NIRS represents a valuable tool for monitoring cerebral autoregulation in neonates affected by perinatal asphyxia, underscoring the utility of assessing endothelial frequency or energy on rScO2 measured by NIRS using the original INVOS™ device frequency.
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Asfixia Neonatal , Circulación Cerebrovascular , Espectroscopía Infrarroja Corta , Humanos , Recién Nacido , Estudios Retrospectivos , Asfixia Neonatal/fisiopatología , Masculino , Femenino , Circulación Cerebrovascular/fisiología , Estudios Longitudinales , Saturación de Oxígeno/fisiología , Imagen por Resonancia Magnética , Hipotermia Inducida , Endotelio Vascular/fisiopatologíaRESUMEN
Viscosity-vaso-occlusion (VVO) and haemolysis-endothelial dysfunction (HED) are pathophysiological mechanisms and clinical subphenotypes of sickle cell disease (SCD). Recurrent vaso-occlusive crises (VOC) may lead to neuroplastic changes and pain sensitization. Among 257 SCD participants, we assessed the relationship of subphenotypes with pain sensitivity using quantitative sensory testing to identify heat pain thresholds (HPT) and pressure pain thresholds (PPT). VOC history and sleep, social and emotional functioning were assessed using the Adult Sickle Cell Quality of Life Measurement Information System. The 'elbow method' determined the optimal number of clusters as three. Clustering was performed using K-prototypes. Among clusters 2 and 3, VOC frequency and severity were higher. Clusters 1 and 3 had lower haemoglobin, higher reticulocytes and lactate dehydrogenase and more leg ulcers. In multivariate regression, cluster 3 was associated with approximately 13.6% lower PPT compared to cluster 1, and female sex was associated with decreases in PPT and HPT at the hands and feet (p < 0.001). Hydroxyurea use and unit increases in sleep functioning and age were associated with approximately 20.1% higher foot-PPT, 6.8% higher hand-PPT and 2.5% higher hand-HPT and foot-HPT respectively. Findings suggest that a third subphenotype with mixed VVO and HED features and worse pain sensitization may exist.
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Anemia de Células Falciformes , Viscosidad Sanguínea , Hemólisis , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Masculino , Femenino , Adulto , Umbral del Dolor , Jamaica , Dolor/etiología , Dolor/fisiopatología , Adulto Joven , Endotelio Vascular/fisiopatología , Persona de Mediana Edad , Adolescente , Calidad de Vida , Pueblos CaribeñosRESUMEN
AIM: This study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration. METHODS: In this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series. RESULTS: Seventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m2, FEV1, 0.79 (0.67-1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels. CONCLUSIONS: Acute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect.
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Beta vulgaris , Estudios Cruzados , Suplementos Dietéticos , Endotelio Vascular , Nitratos , Enfermedad Pulmonar Obstructiva Crónica , Rigidez Vascular , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Masculino , Anciano , Femenino , Nitratos/administración & dosificación , Nitratos/sangre , Nitratos/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Persona de Mediana Edad , Rigidez Vascular/efectos de los fármacos , Rigidez Vascular/fisiología , Arginina/administración & dosificación , Arginina/sangre , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.
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Biomarcadores , COVID-19 , Trombomodulina , Activador de Plasminógeno de Tipo Uroquinasa , Factor de von Willebrand , Humanos , COVID-19/mortalidad , COVID-19/sangre , Masculino , Factor de von Willebrand/metabolismo , Factor de von Willebrand/análisis , Persona de Mediana Edad , Femenino , Biomarcadores/sangre , Anciano , Activador de Plasminógeno de Tipo Uroquinasa/sangre , Trombomodulina/sangre , Estudios Prospectivos , Pronóstico , SARS-CoV-2 , Adulto , Endotelio Vascular/fisiopatología , Mortalidad Hospitalaria , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.
ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.
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Endotelio Vascular , Termografía , Humanos , Termografía/métodos , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Endotelio Vascular/fisiopatología , Adulto , Anciano , Factores de Riesgo de Enfermedad Cardiaca , Sensibilidad y Especificidad , Rayos Infrarrojos , Arteria Braquial/fisiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Vasodilatación/fisiología , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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COVID-19 , Unidades de Cuidados Intensivos/estadística & datos numéricos , Neumonía Viral , Complicaciones Infecciosas del Embarazo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/terapia , Estudios de Cohortes , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Edad Gestacional , Humanos , México/epidemiología , Mortalidad , Placenta/metabolismo , Placenta/fisiopatología , Factor de Crecimiento Placentario/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/etiología , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/terapia , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la EnfermedadRESUMEN
Preeclampsia (PE) is a specific syndrome of human pregnancy, being one of the main causes of maternal death. Persistent inflammation in the endothelium stimulates the secretion of several inflammatory mediators, activating different signaling patterns. One of these mechanisms is related to NLRP3 activation, initiated by high levels of danger signals such as cholesterol, urate, and glucose, producing IL-1, IL-18, and cell death by pyroptosis. Furthermore, reactive oxygen species (ROS), act as an intermediate to activate NLRP3, contributing to subsequent inflammatory cascades and cell damage. Moreover, increased production of ROS may elevate nitric oxide (NO) catabolism and consequently decrease NO bioavailability. NO has many roles in immune responses, including the regulation of signaling cascades. At the site of inflammation, vascular endothelium is crucial in the regulation of systemic inflammation with important implications for homeostasis. In this review, we present the important role of NLRP3 activation in exacerbating oxidative stress and endothelial dysfunction. Considering that the causes related to these processes and inflammation in PE remain a challenge for clinical practice, the use of drugs related to inhibition of the NLRP3 may be a good option for future solutions for this disease.
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Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo , Preeclampsia/tratamiento farmacológico , Preeclampsia/fisiopatología , Femenino , Humanos , Inflamasomas/metabolismo , Modelos Biológicos , Preeclampsia/patología , EmbarazoRESUMEN
Arterial endothelial dysfunction has been extensively studied in heart failure (HF). However, little is known about the adjustments shown by the venous system in this condition. Considering that inferior vena cava (VC) tone could influence cardiac performance and HF prognosis, the aim of the present study was to assess the VC and thoracic aorta (TA) endothelial function of HF-post-myocardial infarction (MI) rats, comparing both endothelial responses and signaling pathways developed. Vascular reactivity of TA and VC from HF post-MI and sham operated (SO) rats was assessed with a wire myograph, 4 weeks after coronary artery occlusion surgery. Nitric oxide (NO), H2O2 production and oxidative stress were evaluated in situ with fluorescent probes, while protein expression and dimer/monomer ratio was assessed by Western blot. VC from HF rats presented endothelial dysfunction, while TA exhibited higher acetylcholine (ACh)-induced vasodilation when compared with vessels from SO rats. TA exhibited increased ACh-induced NO production due to a higher coupling of endothelial and neuronal NO synthases isoforms (eNOS, nNOS), and enhanced expression of antioxidant enzymes. These adjustments, however, were absent in VC of HF post-MI rats, which exhibited uncoupled nNOS, oxidative stress and higher H2O2 bioavailability. Altogether, the present study suggests a differential regulation of endothelial function between VC and TA of HF post-MI rats, most likely due to nNOS uncoupling and compromised antioxidant defense.
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Aorta Torácica/fisiopatología , Endotelio Vascular/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Óxido Nítrico Sintasa/metabolismo , Vena Cava Inferior/fisiopatología , Animales , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Peróxido de Hidrógeno/metabolismo , Masculino , Infarto del Miocardio/complicaciones , Estrés Oxidativo , Ratas Wistar , Vena Cava Inferior/enzimologíaRESUMEN
INTRODUCTION: Exercise training is strongly recommended as a therapeutic approach to treat individuals with heart failure. High-intensity exercise training modalities still controversial in this population. The study aims to preliminary assess the consequences of high-intensity exercise training modalities, aerobic interval training (HIIT) and progressive high circuit-resistance training (CRT), on primarily endothelial function and cardiorespiratory fitness, and secondly on muscle strength and physical performance in heart failure patients. METHODS: This preliminary multicentric randomized controlled trial comprised 23 heart failure patients, aged 56 ± 10 years old, mainly New York Heart Association classification I and II (%), hemodynamically stable, who compromise at least 36 exercise sessions of a randomly assigned intervention (HIIT, CRT or control group). Endothelial function, cardiopulmonary exercise testing, muscle strength and physical performance were completed at baseline and post-intervention. RESULTS: Although no effects on endothelial function; both HIIT and CRT modalities were able to produce a positive effect on [Formula: see text] peak (HIIT = +2.1±6.5, CRT = +3.0±4.2 and control group = -0.1± 5.3 mL/kg/min, time*group p-value<0,05) and METs (HIIT = +0.6±1.8, CRT = +0.9±1.2 and control group = 0±1.6, time*group p-value<0,05). Only HIIT increased isokinetic torque peak (HIIT = +8.8±55.8, CRT = 0.0±60.7 and control group = 1.6±57.6 Nm) matched p-value<0,05. Regarding the physical performance, the CRT modality reduced chair stand test completion time (HIIT = -0.7±3.1, CRT = -3.3±3.2 and control group = -0.3±2.5 s, matched p-value<0,05 and HIIT improved global physical performance(time*group p<0,05). CONCLUSION: This preliminary study trends to indicate for the first time that high-intensity interval training promotes a jointly superior effect compared to progressive high intensity circuit-resistance training by improving cardiorespiratory fitness, muscular strength, and physical performance. Further research with larger cohort is necessary. CLINICAL TRIAL REGISTRATION NUMBER: ReBEC RBR-668c8v.
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Capacidad Cardiovascular/fisiología , Ejercicio en Circuitos , Endotelio Vascular/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Entrenamiento de Intervalos de Alta Intensidad , Entrenamiento de Fuerza , Anciano , Composición Corporal/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Resultado del TratamientoRESUMEN
Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.
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Ácidos Nucleicos Libres de Células/sangre , Endotelio Vascular/fisiopatología , Envejecimiento , Biomarcadores/sangre , Diabetes Mellitus , Endotelio Vascular/metabolismo , Humanos , Hipertensión , Conducta Sedentaria , FumarRESUMEN
BACKGROUND: The mechanisms underlying functional impairments in symptomatic PAD patients are controversial and poorly understood. Endothelial dysfunction and arterial stiffness have been proposed as potential mechanisms related to functional impairment in symptomatic PAD patients, however, more studies are needed to confirm these associations. OBJECTIVE: To analyze the association between vascular function and walking impairment in patients with peripheral arterial disease (PAD) and symptoms of claudication. METHODS: This was a cross-sectional study that included 68 patients with symptomatic PAD. All patients underwent an objective (Six-minute walk test [6MWT], 4-meter walk test) and a subjective (Walking Impairment Questionnaire [WIQ]) measurement of walking impairment. Vascular parameters measured were pulse-wave velocity (PWV) and flow-mediated dilation (FMD). Multiple linear regression was performed to investigate the association among walking impairment variables with vascular function parameters. RESULTS: No significant associations between the claudication onset distance (PWV: b=.060, P = 0.842; FMD: b=-.192, P = 0.456), 6MWT (PWV: b=.007, P = 0..975; FMD: b=.090, P = 0.725), WIQ distance (PWV: b=.337, P = 0.117; FMD: b=-.025, P = 0.895) WIQ speed (PWV: b=.320, P = 0.181; FMD: b=-.028, P = 0.497), WIQ stairs (PWV: b=.256, P = 0.204; FMD: b=-.228, P = 0.230), 4-meter usual walk (PWV: b=-.421, P = 0.107; FMD: b=-.338, P = 0.112), 4-meter fast walk (PWV: b=-.496, P = 0.063; FMD: b=-.371, P = 0.086) and vascular function were found. CONCLUSIONS: In symptomatic PAD patients, vascular function is not associated to walking impairment, even when adjusting for comorbid conditions and diabetes.
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Endotelio Vascular/fisiopatología , Claudicación Intermitente/fisiopatología , Enfermedad Arterial Periférica/fisiopatología , Rigidez Vascular , Vasodilatación , Caminata , Anciano , Comorbilidad , Estudios Transversales , Tolerancia al Ejercicio , Femenino , Humanos , Claudicación Intermitente/diagnóstico , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Valor Predictivo de las Pruebas , Análisis de la Onda del Pulso , Encuestas y Cuestionarios , Prueba de PasoRESUMEN
Intravascular hemolysis (IH) contributes to the development of endothelial dysfunction (ED) in sickle cell anemia (SCA), and the effects of hydroxyurea (HU, the only approved drug that decreases the frequency and severity of vaso-oclussive crises) on IH and ED in SCA remain unclear. We evaluated and compared the markers of IH among steady-state adult Brazilians with SCA and HbAA individuals. Overall, this cross-sectional study enrolled 30 SCA patients not receiving HU therapy (HbSS), 25 SCA patients receiving HU therapy (HbSS_HU), and 32 HbAA volunteers (HbAA). The IH markers evaluated were serum Lactate Dehydrogenase (LDH), total heme, plasma hemoglobin (pHb), and soluble CD163 (sCD163). The ED markers analyzed were plasma von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo) levels, antigen of VWF-cleaving protease (ADAMTS13:Ag), thrombospondin-1, endothelin-1 levels, and ADAMTS13 Activity (ADAMTS13:Act). The levels of VWF:Ag, VWF:RCo, total heme, thrombospondin-1, and endothelin-1 were significantly higher in SCA patients (HbSS and HbSS_HU) compared to HbAA individuals. Also, pHb, LDH, and thrombospondin-1 levels were significantly higher in the HbSS group than in the HbSS_HU group. Contrarily, the levels of sCD163, ADAMTS13:Ag, and ADAMTS13:Act were significantly lower in both groups of SCA patients than HbAA controls, and ADAMTS13:Act levels were significantly lower in HbSS compared to HbSS_HU patients. The higher ADAMTS13 activity levels in those on HU therapy may be attributed to lower pHb and thrombospondin-1 levels as previously shown by in vitro studies that thrombospondin-1 and pHb are bound to VWF. Thus, VWF is restrained from ADAMTS13 activity and cleavage.
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Anemia de Células Falciformes/tratamiento farmacológico , Endotelio Vascular/fisiopatología , Hemólisis/efectos de los fármacos , Hidroxiurea/uso terapéutico , Proteína ADAMTS13/sangre , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores , Estudios Transversales , Endotelio Vascular/efectos de los fármacos , Femenino , Hemo/análisis , Hemoglobinas/análisis , Humanos , Hidroxiurea/farmacología , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Prohibitinas , Receptores de Superficie Celular/sangre , Trombospondina 1/sangre , Adulto Joven , Factor de von Willebrand/análisisRESUMEN
Headache is the most common neurological symptom in COVID-19, reported in 6.5 to 34% of patients. Few studies have analyzed its characteristics, and some of them included cases without laboratory confirmation or reported only critical patients. We aimed to analyze the clinical characteristics of COVID-19 associated headache in laboratory-confirmed cases. We conducted a retrospective evaluation of patients with COVID-19 and neurological symptoms. Patients who reported headache answered an interview about its clinical characteristics. Twenty-four patients with COVID-19 associated headache completed the interview. Mean age of patients was 53.8 (standard deviation-17.44), and 14 out of 24 (58.3%) were male. The majority (75%) had no previous history of headache. Fever was documented in 19 out of the 24 patients (79.1%). Headache was predominantly bifrontal or holocranial, in pressure, during hours, worsening with cough or physical activity. COVID-19 headache tends to appear in the first days of symptoms, be either frontal or holocranial and last for days. The quality of pain in pressure and the worsening with cough or physical activity were reported in most cases. We have not found any characteristic that could differentiate COVID-19 associated headache from other causes of headache, possibly because of its multifactorial mechanism.
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COVID-19/complicaciones , Cefalea/etiología , SARS-CoV-2 , Adolescente , Adulto , Antihipertensivos/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de COVID-19 , Comorbilidad , Citocinas/fisiología , Endotelio Vascular/fisiopatología , Endotelio Vascular/virología , Femenino , Fiebre/etiología , Cefalea/fisiopatología , Humanos , Inflamación , Masculino , Modelos Biológicos , Neoplasias/epidemiología , Estudios Retrospectivos , Evaluación de Síntomas , Nervio Trigémino/virología , Adulto JovenRESUMEN
Coronary artery disease (CAD) and its complications are the leading cause of death worldwide. Inflammatory activation and dysfunction of the endothelium are key events in the development and pathophysiology of atherosclerosis and are associated with an elevated risk of cardiovascular events. There is great interest to further understand the pathophysiologic mechanisms underlying endothelial dysfunction and atherosclerosis progression, and to identify novel biomarkers and therapeutic strategies to prevent endothelial dysfunction, atherosclerosis and to reduce the risk of developing CAD and its complications. The use of liquid biopsies and new molecular biology techniques have allowed the identification of a growing list of molecular and cellular markers of endothelial dysfunction, which have provided insight on the molecular basis of atherosclerosis and are potential biomarkers and therapeutic targets for the prevention and or treatment of atherosclerosis and CAD. This review describes recent information on normal vascular endothelium function, as well as traditional and novel potential biomarkers of endothelial dysfunction and inflammation, and pharmacological and non-pharmacological therapeutic strategies aimed to protect the endothelium or reverse endothelial damage, as a preventive treatment for CAD and related complications.
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Biomarcadores , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Vasculitis/etiología , Vasculitis/metabolismo , Animales , Permeabilidad Capilar , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/fisiopatología , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Hemostasis , Humanos , Terapia Molecular Dirigida/métodos , Vasculitis/tratamiento farmacológico , Vasculitis/fisiopatologíaRESUMEN
BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.
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Compuestos de Bencidrilo/uso terapéutico , Glucemia/efectos de los fármacos , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Glucósidos/uso terapéutico , Gliburida/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Vasodilatación/efectos de los fármacos , Adulto , Anciano , Compuestos de Bencidrilo/efectos adversos , Biomarcadores/sangre , Glucemia/metabolismo , Brasil , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Quimioterapia Combinada , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Glucósidos/efectos adversos , Gliburida/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Gestational diabetes mellitus (GDM) affects 5-10% of pregnancies and increases the risk of fetal and maternal adverse outcomes. Interestingly, the vascular response to AngII is decreased by pregnancy while the response is increased by diabetes. It remains unclear how GDM affects vascular tone and how angiotensin II receptors contribute to these changes. In this work, we sought to establish the vascular impact of a hypercaloric diet-induced GDM through changes in AT1 and AT2 receptor's expression. Female rats fed for 7 weeks with standard (SD) or hypercaloric (HD) diet were divided at week 4. Half of the rats of each group were mated to become pregnant and those fed with a HD developed GDM. AngII-induced vasoconstriction was measured in thoracic or abdominal aorta rings using a conventional isolated organ bath and AT1 and AT2 receptors were searched by immunohistochemistry. Experiments where conducted on the pregnant standard diet group (PSD) and the pregnant hypercaloric-gestational diabetes mellitus group (PHD-GDM). Vasoconstriction was reduced in the thoracic aorta (P < 0.05 vs PSD) but increased in the abdominal aorta of PHD-GDM rats (P < 0.05 vs PSD). Blockade of AT2 receptors using PD123319 decreased vasoconstriction, particularly in the abdominal aorta of PHD-GDM animals (P < 0.05 vs PSD). PHD-GDM increased AT1 receptors expression (P < 0.05 vs PSD). Also, PHD-GDM reverted physiologic hypoglycemia and hypotension of healthy pregnancy. Findings provide new insight into the hypercaloric diet induced damage on the vasculature during pregnancy.
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Aorta Abdominal/metabolismo , Aorta Torácica/metabolismo , Diabetes Gestacional/metabolismo , Endotelio Vascular/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Vasoconstricción , Angiotensina II/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Animales , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/fisiopatología , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiopatología , Diabetes Gestacional/fisiopatología , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Embarazo , Ratas Wistar , Receptor de Angiotensina Tipo 1/agonistas , Receptor de Angiotensina Tipo 2/agonistas , Transducción de Señal , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacologíaRESUMEN
OBJECTIVES: To summarize existing evidence and quantify the effects of physical activity on vascular function and structure in autoimmune rheumatic diseases (ARDs). METHODS: Databases were searched (through March 2020) for clinical trials evaluating the effects of physical activity interventions on markers of micro- and macrovascular function and macrovascular structure in ARDs. Studies were combined using random effects meta-analysis, which was conducted using Hedges' g. Meta-analyses were performed on each of the following outcomes: microvascular function [i.e. skin blood flow or vascular conductance responses to acetylcholine (ACh) or sodium nitropusside (SNP) administration]; macrovascular function [i.e. brachial flow-mediated dilation (FMD%) or brachial responses to glyceryl trinitrate (GTN%); and macrovascular structure [i.e. aortic pulse wave velocity (PWV)]. RESULTS: Ten studies (11 trials) with a total of 355 participants were included in this review. Physical activity promoted significant improvements in microvascular [skin blood flow responses to ACh, g = 0.92 (95% CI 0.42, 1.42)] and macrovascular function [FMD%, g = 0.94 (95% CI 0.56, 1.02); GTN%, g = 0.53 (95% CI 0.09, 0.98)]. Conversely, there was no evidence for beneficial effects of physical activity on macrovascular structure [PWV, g = -0.41 (95% CI -1.13, 0.32)]. CONCLUSIONS: Overall, the available clinical trials demonstrated a beneficial effect of physical activity on markers of micro- and macrovascular function but not on macrovascular structure in patients with ARDs. The broad beneficial impact of physical activity across the vasculature identified in this review support its role as an effective non-pharmacological management strategy for patients with ARDs.
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Enfermedades Autoinmunes/fisiopatología , Endotelio Vascular/fisiopatología , Ejercicio Físico/fisiología , Microvasos/fisiopatología , Enfermedades Reumáticas/fisiopatología , Humanos , Microcirculación , Análisis de la Onda del Pulso , Flujo Sanguíneo Regional , Vasodilatación/fisiología , VasodilatadoresRESUMEN
BACKGROUND: Aerobic exercise improves endothelial function and arterial stiffness after myocardial infarction (MI), but the effects of isometric exercise on cardiovascular parameters are still uncertain. We aimed to assess the effects of one session of aerobic or isometric exercise on flow-mediated dilation (FMD) and pulse wave velocity (PWV) in post-MI volunteers undergoing percutaneous coronary intervention (PCI). METHODS: Twenty post-MI patients undergoing PCI were randomized to aerobic (AE, n = 10) or isometric (IE, n = 10) exercise groups. We evaluated cardiac structure and function (echocardiographic); carotid plaque presence (ultrasound). FMD and PWV were measured 10 min before and 10 min after the intervention: a single session of moderate-intensity AE (30 min; ratings 12-14 on Borg's scale or 50-60% HRreserve) or handgrip IE (four two-minute bilateral contractions; 30% maximal voluntary contraction; 1-min rest). Generalized estimating equations (Bonferroni post-hoc) was used to assess differences (p ≤ 0.050). RESULTS: FMD improved only in the AE group (Δ = 4.9%; p = 0.034), with no difference between groups after exercise. Even after adjustment (for baseline brachial artery diameter) the effectiveness of AE remained (p = 0.025) with no change in the IE group. PWV was slightly reduced from baseline in the AE group (Δ = 0.61 m/s; p = 0.044), and no difference when compared to the IE group. Peripheral vascular resistance decreased in AE versus IE (p = 0.050) and from baseline (p = 0.014). CONCLUSIONS: Vascular measurements (FMD and PWV) improved after a single session of AE. There are apparently no benefits following a session of IE. TRIAL REGISTRATION: http://www.clinicaltrials.gov and ID number NCT04000893.
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Arteria Braquial/fisiopatología , Endotelio Vascular/fisiopatología , Terapia por Ejercicio , Fuerza de la Mano , Contracción Isométrica , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/terapia , Rigidez Vascular , Vasodilatación , Anciano , Presión Arterial , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Proyectos Piloto , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Resistencia VascularRESUMEN
Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Cholesterol levels and oxidative stress are key contributors to endothelial damage, whereas high levels of plasma high-density lipoproteins (HDL) could prevent it. Cholesteryl ester transfer protein (CETP) is one of the most potent endogenous negative regulators of HDL-cholesterol. However, whether and to what degree CETP expression impacts endothelial function, and the molecular mechanisms underlying the vascular effects of CETP on endothelial cells, have not been addressed. Acetylcholine-induced endothelium-dependent relaxation of aortic rings was impaired in human CETP-expressing transgenic mice, compared to their non-transgenic littermates. However, endothelial nitric oxide synthase (eNOS) activation was enhanced. The generation of superoxide and hydrogen peroxide was increased in aortas from CETP transgenic mice, while silencing CETP in cultured human aortic endothelial cells effectively decreased oxidative stress promoted by all major sources of ROS: mitochondria and NOX2. The endoplasmic reticulum stress markers, known as GADD153, PERK, and ARF6, and unfolded protein response effectors, were also diminished. Silencing CETP reduced endothelial tumor necrosis factor (TNF) α levels, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression, diminishing monocyte adhesion. These results support the notion that CETP expression negatively impacts endothelial cell function, revealing a new mechanism that might contribute to atherosclerosis.