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BACKGROUND: Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. METHODS: This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0 ± 11.8 years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI < 1.0 was classified as poor endothelial function, and an ABI < 0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. RESULTS: Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04 ± 0.16 vs. 1.08 ± 0.15, P = 0.028 for the right ABI; 1.01 ± 0.16 vs. 1.06 ± 0.16, P = 0.002 for the left ABI) and VRI (0.83 ± 0.57 vs. 1.08 ± 0.56, P < 0.001) and had higher serum levels of ICAM-1 (P < 0.001), VCAM-1 (P = 0.003) and ET-1 (P = 0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P = 0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P = 0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. CONCLUSIONS: Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.
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Enfermedad Arterial Periférica , Insuficiencia Renal Crónica , Sarcopenia , Humanos , Sarcopenia/fisiopatología , Sarcopenia/etiología , Anciano , Femenino , Masculino , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Estudios Transversales , Biomarcadores/sangre , Endotelio Vascular/fisiopatología , Persona de Mediana EdadRESUMEN
INTRODUCTION: SARS-CoV-2 infection causes severe endothelial damage, an essential step for cardiovascular complications. Endothelial-colony forming cells (ECFCs) act as a biomarker of vascular damage but their role in SARS-CoV-2 remain unclear. The aim of this study was to assess whether the number of ECFCs and angiogenic biomarkers remained altered after 6 and 12-months post-infection and whether this imbalance correlated with the presence of long-COVID syndrome and other biological parameters measured. METHODS: Seventy-two patients were recruited at different time-points after overcoming COVID-19 and thirty-one healthy controls. All subjects were matched for age, gender, BMI, and comorbidities. ECFCs were obtained from peripheral blood and cultured with specific conditions. RESULTS: The results confirm the presence of a long-term sequela in post-COVID-19 patients, with an abnormal increase in ECFC production compared to controls (82.8% vs. 48.4%, P < 0.01) that is maintained up to 6-months (87.0% vs. 48.4%, P < 0.01) and 12-months post-infection (85.0% vs. 48.4%, P < 0.01). Interestingly, post-COVID-19 patients showed a significant downregulation of angiogenesis-related proteins compared to controls indicating a clear endothelial injury. Troponin, NT-proBNP and ferritin levels, markers of cardiovascular risk and inflammation, remained elevated up to 12-months post-infection. Patients with lower numbers of ECFC exhibited higher levels of inflammatory markers, such as ferritin, suggesting that ECFCs may play a protective role. Additionally, long-COVID syndrome was associated with higher ferritin levels and with female gender. CONCLUSIONS: These findings highlight the presence of vascular sequela that last up to 6- and 12-months post-infection and point out the need for preventive measures and patient follow-up.
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COVID-19 , Enfermedades Cardiovasculares , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/fisiopatología , COVID-19/sangre , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Endotelio Vascular/fisiopatología , Anciano , Adulto , Biomarcadores/sangre , Células Progenitoras Endoteliales , Estudios de Casos y Controles , Síndrome Post Agudo de COVID-19RESUMEN
Since the beginning of the pandemic, both COVID-19-associated coagulopathy biomarkers and a plethora of endothelial biomarkers have been proposed and tested as prognostic tools of severity and mortality prediction. As the pandemic is gradually being controlled, attention is now focusing on the long-term sequelae of COVID-19. In the present study, we investigated the role of endothelial activation/dysfunction in long COVID syndrome. This observational study included 68 consecutive long COVID patients and a healthy age and sex-matched control group. In both groups, we measured 13 endothelial biomarkers. Moreover, in the long COVID patients, we evaluated fatigue and dyspnea severity, lung diffusion capacity (DLCO), and the 6-min walk (6MWT) test as measures of functional capacity. Our results showed that markers of endothelial activation/dysfunction were higher in long COVID patients, and that soluble intracellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) negatively correlated with lung diffusion and functional capacity (sICAM-1 vs. DLCO, r = -0.306, p = 0.018; vs. 6MWT, r = -0.263, p = 0.044; and sVCAM-1 vs. DLCO, r= -0.346, p = 0.008; vs. 6MWT, r = -0.504, p < 0.0001). In conclusion, evaluating endothelial biomarkers alongside clinical tests might yield more specific insights into the pathophysiological mechanisms of long COVID manifestations.
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Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.
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MicroARNs , Sepsis Neonatal , Sepsis , Humanos , Recién Nacido , Lactante , MicroARNs/genética , Sepsis Neonatal/diagnóstico , Interleucina-18 , Factor A de Crecimiento Endotelial Vascular , Biomarcadores/metabolismo , Sepsis/diagnóstico , Sepsis/genética , InflamaciónRESUMEN
Systemic lupus erythematosus is a connective disease in which all vitally important organs may be affected. The etiology of the disease is largely unknown and almost all immunological mechanisms have been proposed as the pathophysiological background of the disease. Among them, endothelial damage and dysfunction seem to play a pivotal role. Endothelial damage can be accurately measured using adhesion molecules such asintercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), platelet endothelial cell adhesion molecule (PECAM) and selectins. In this review we discuss the role of well-known cellular adhesion molecules as pathogenic factors in disease development as well as disease activity biomarkers.
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Background: COVID-19 is characterized by endothelial dysfunction and is presumed to have long-term cardiovascular sequelae. In this cross-sectional study, we aimed to explore the serum levels of endothelial biomarkers in patients who recovered from COVID-19 one year after hospital discharge. Methods: In this clinical follow-up study, 345 COVID-19 survivors from Huanggang, Hubei, and 119 age and gender-matched medical staff as healthy controls were enrolled. A standardized symptom questionnaire was performed, while electrocardiogram and Doppler ultrasound of lower extremities, routine blood tests, biochemical and immunological tests, serum soluble vascular cell adhesion molecule-1(VCAM-1), intercellular cell adhesion molecule-1(ICAM-1), P-selectin, and fractalkine were measured by enzyme-linked immunosorbent assays (ELISA). Results: At one year after discharge, 39% of recovers possessed post-COVID syndromes, while a few had abnormal electrocardiogram manifestations, and no deep vein thrombosis was detected in all screened survivors. There were no significant differences in circulatory inflammatory markers (leukocytes, neutrophils, lymphocytes, C-reactive protein and interleukin-6), alanine aminotransferase, estimated glomerular filtration rate, glucose, triglycerides, total cholesterol and D-dimer observed among healthy controls with previously mild or severe infected. Furthermore, serum levels of VCAM-1, ICAM-1, P-selectin, and fractalkine do not significantly differ between survivors and healthy controls. Conclusions: SARS-CoV-2 infection may not impose a higher risk of developing long-term cardiovascular events, even for those recovering from severe illness.
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BACKGROUND: Approaches to the evaluation of pulmonary arterial hypertension (PAH) in premature calves by using lung-specific epithelial and endothelial biomarkers are needed. OBJECTIVE: To investigate the evaluation of PAH in premature calves with and without respiratory distress syndrome (RDS) by using lung-specific epithelial and endothelial biomarkers and determine the prognostic value of these markers in premature calves. ANIMALS: Fifty premature calves with RDS, 20 non-RDS premature calves, and 10 healthy term calves. METHODS: Hypoxia, hypercapnia, and tachypnea were considered criteria for RDS. Arterial blood gases (PaO2 , PaCO2 , oxygen saturation [SO2 ], base excess [BE], and serum lactate concentration) were measured to assess hypoxia. Serum concentrations of lung-specific growth differentiation factor-15 (GDF-15), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and surfactant protein D (SP-D) were measured to assess PAH. RESULTS: Arterial blood pH, PaO2 , SO2 , and BE of premature calves with RDS were significantly lower and PaCO2 and lactate concentrations higher compared to non-RDS premature and healthy calves. The ADMA and SP-D concentrations of premature calves with RDS were lower and serum ET-1 concentrations higher than those of non-RDS premature and healthy calves. No statistical differences for GDF-15 and VEGF were found among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Significant increases in serum ET-1 concentrations and decreases in ADMA and SP-D concentrations highlight the utility of these markers in the diagnosis of PAH in premature calves with RDS. Also, we found that ET-1 was a reliable diagnostic and prognostic biomarker for PAH and predicting mortality in premature calves.
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Síndrome de Dificultad Respiratoria del Recién Nacido , Factor A de Crecimiento Endotelial Vascular , Animales , Biomarcadores , Bovinos , Recién Nacido , Pulmón , Proteína D Asociada a Surfactante Pulmonar , Síndrome de Dificultad Respiratoria del Recién Nacido/veterinariaRESUMEN
Acute kidney injury (AKI) is a frequent and potentially fatal complication of snakebites. In the setting of snakebites, endothelial biomarkers may be used to predict disease severity and can play a major role in AKI pathophysiology. The aim of this study was to investigate the potential role of endothelial biomarkers in predicting AKI in Bothrops envenoming. Therefore, blood and urine samples were collected from 26 patients admitted to the emergency department after Bothrops envenoming at 3 different post-bite points in time: on admission (up to 8â¯h post-bite), 12-16â¯h, and 24-28â¯h post-bite, to investigate the time course of endothelial biomarkers in AKI following Bothrops snakebites. The diagnostic performance of injury biomarkers in Bothrops envenomation was evaluated. AKI was diagnosed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. There was an association between endothelial injury and increased risk for AKI in bothropic envenoming. Angiopoietin- 1 (Ang-1) and Vascular cell adhesion protein-1 (VCAM-1) were useful biomarkers to predict mild AKI [AUC-ROC: Ang-1 0.82, VCAM-1 0.76] within the interval of 8-16 h post Bothrops snakebites. The use of endothelial biomarkers VCAM-1 e Ang-1 within 12-16 h post-bite may be useful in the early stage of mild AKI related to Bothrops envenoming and might have an effect on the early intervention for renal protection in less severe Bothrops-related AKI.
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Lesión Renal Aguda/etiología , Angiopoyetina 1/sangre , Bothrops , Venenos de Crotálidos/metabolismo , Células Endoteliales/metabolismo , Riñón/metabolismo , Mordeduras de Serpientes/complicaciones , Molécula 1 de Adhesión Celular Vascular/sangre , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Adulto , Animales , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Mordeduras de Serpientes/metabolismo , Factores de TiempoRESUMEN
INTRODUCTION: Endothelial dysfunction plays an essential role in the pathogenesis of sepsis. The study aimed to illustrate the associations between the dynamic change (from day 1 to day 7) in biomarker concentration of endothelial dysfunction and outcomes in severe sepsis and septic shock in the intensive care unit (ICU). MATERIALS AND METHODS: We studied 102 patients enrolled in the Beijing Chao-yang Hospital affiliated with the Capital Medical University. A receiver operating characteristic (ROC) curve were used to assess the prognostic values of the circulating adhesion Angiopoietin-2/Angiopoietin-1 ratio (Ang-2/Ang-1) and Angiopoietin-1/Tie-2 ratio (Ang-1/Tie-2), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and thrombomodulin (TM). Spearman's rank correlation and a multiple regression analysis were used to assess the relationship between the change in sequential organ failure assessment (Δ SOFA) score (SOFA score at day 7 minus SOFA score at day 1) and the levels of Δ Ang-2/Ang-1 and Δ Ang-1/Tie-2 ratios, ΔsICAM-1, ΔsVCAM-1 and Δ sTM. RESULTS: The Ang-2/Ang-1 ratio, sICAM-1, sVCAM-1 and sTM levels significantly increased from day 1 to day 7 (all pâ¯=â¯0.045), and the Ang-1/Tie-2 ratio level markedly decreased from day 1 and day 7 (pâ¯=â¯0.027) in non-survivors. The biomarkers at Days 1 and 7 had significant prognostic value for 90-day mortality in severe sepsis and septic shock in ICU. The difference in biomarkers for endothelial dysfunction were suggested to be effective, independent predictors of changes in Δ SOFA. CONCLUSIONS: Endothelial dysfunction may constitute an independent contributor to sepsis-associated outcomes in ICU.
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Biomarcadores/sangre , Sepsis/sangre , Choque Séptico/sangre , Anciano , Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Cuidados Críticos , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Receptor TIE-2/sangre , Sepsis/diagnóstico , Sepsis/mortalidad , Choque Séptico/diagnóstico , Choque Séptico/mortalidad , Trombomodulina/sangre , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
PURPOSE: We investigated whether impaired flow-mediated dilation (FMD) and plasma biomarkers reflecting endothelial dysfunction are associated with coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease (CAD). METHODS: Patients (n = 194) were randomly selected women with angina pectoris and no obstructive CAD (<50% stenosis). A reference population of asymptomatic women without CAD (n = 25) was included. We measured FMD in the brachial artery by high-resolution ultrasound. Coronary flow velocity reserve (CFVR) was assessed by transthoracic Doppler flow echocardiography (TTDE) of the left anterior descending artery during rest and high-dose dipyridamole infusion. CMD was defined as CFVR <2. RESULTS: FMD and CFVR were measured in 128 patients and 21 controls. Mean (SD) age was 64.5 (8.9) years, mean CFVR was 2.3 (2.0-2.7), and mean FMD was 8.4% (4.8%) in angina patients. Angina patients had a higher risk factor burden compared with the reference population. Measures of peripheral endothelial dysfunction and endothelial plasma biomarkers did not differ according to angina or CFVR. CFVR and FMD did not correlate (Spearman ρ = -0.07, p = 0.45). CONCLUSIONS: FMD and biomarkers of endothelial dysfunction did not identify individuals with CMD assessed as impaired CFVR by TTDE in women with angina and no obstructive CAD.
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Angina de Pecho/fisiopatología , Arteria Braquial/fisiopatología , Estenosis Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Endotelio Vascular/fisiopatología , Reserva del Flujo Fraccional Miocárdico , Vasodilatación , Anciano , Angina de Pecho/diagnóstico , Angina de Pecho/etiología , Velocidad del Flujo Sanguíneo , Arteria Braquial/diagnóstico por imagen , Estenosis Coronaria/complicaciones , Estenosis Coronaria/diagnóstico por imagen , Dipiridamol/administración & dosificación , Ecocardiografía Doppler , Femenino , Humanos , Microcirculación , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vasodilatadores/administración & dosificaciónRESUMEN
Low-carbohydrate diets (LCD) are increasing in popularity, but their effect on vascular health has been questioned. Endothelial microvesicles (EMV) are membrane-derived vesicles with the potential to act as a sensitive prognostic biomarker of vascular health and endothelial function. The aim of this study was to examine the influence of a LCD on EMV and other endothelial biomarkers of protein origin. Twenty-four overweight women (age, 48.4 ± 0.6 years; height, 1.60 ± 0.07 m; body mass, 76.5 ± 9.1 kg; body mass index, 28.1 ± 2.7 kg·m(-2); waist circumference, 84.1 ± 7.4 cm; mean ± standard deviation) were randomised to either 24 weeks on their normal diet (ND) or a LCD, after which they crossed over to 24 weeks on the alternative diet. Participants were assisted in reducing carbohydrate intake, but not below 40 g·day(-1). Body composition and endothelial biomarkers were assessed at the crossover point and at the end of the study. Daily carbohydrate intake (87 ± 7 versus 179 ± 11 g) and the percentage of energy derived from carbohydrate (29% versus 44%) were lower (p < 0.05) on the LCD compared to the ND, but absolute fat and saturated fat intake were unchanged. Body mass and waist circumference were 3.7 ± 0.8 kg and 3.5 ± 1.0 cm lower (p < 0.05), respectively, after the LCD compared with the ND phases. CD31(+)CD41(-)EMV, soluble (s) thrombomodulin, sE-selectin, sP-selectin, serum amyloid A and C-reactive protein were lower (p < 0.05) after the LCD compared to the ND, but serum lipids and apolipoproteins were not different. EMV along with a range of endothelial and inflammatory biomarkers are reduced by a LCD that involves modest weight loss.
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Dieta Baja en Carbohidratos , Endotelio Vascular/metabolismo , Microvasos/metabolismo , Sobrepeso , Apolipoproteínas/sangre , Biomarcadores/sangre , Composición Corporal , Índice de Masa Corporal , Peso Corporal , Proteína C-Reactiva/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Cruzados , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/análisis , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/análisis , Selectina E/sangre , Ingestión de Energía , Ejercicio Físico , Ácidos Grasos/administración & dosificación , Ácidos Grasos/análisis , Femenino , Humanos , Persona de Mediana Edad , Selectina-P/sangre , Proteína Amiloide A Sérica/metabolismo , Trombomodulina/sangre , Triglicéridos/sangre , Circunferencia de la Cintura , Pérdida de PesoRESUMEN
AIM: To investigate pro-atherosclerotic markers (endothelial dysfunction and inflammation) in patients one year after liver transplantation. METHODS: Forty-four consecutive liver transplant (LT) outpatients who were admitted between August 2009 and July 2010, were followed-up by for 1 year, exhibited no evidences of infection or rejection, all of them underwent tacrolimus-based immunosuppressive regimens were consecutively enrolled. Inflammatory cytokines (TNFα, IFNγ, IL-8, and IL-10), endothelial biomarkers (sVCAM-1, sICAM-1, MPO, adiponectin, PAI-1, SAP, SAA, E-selectin, and MMP-9), high sensitive C-reactive protein, and Framingham risk score (FRS) were assessed. The anthropometric data, aminotransferases, metabolic syndrome features, glucose and lipid profiles, and insulin resistance data were also collected. The LT recipients were compared to 22 biopsy-proven non-alcoholic steatohepatitis (NASH) patients and 20 healthy controls (non-obese, non-diabetics, and non-dyslipidemic). RESULTS: The LT recipients had significantly younger ages and lower body mass indices, aminotransferases, fasting glucose and insulin levels, glucose homeostasis model and metabolic syndrome features than the NASH patients. Classic cardiovascular risk markers, such as Hs-CRP and FRS [2.0 (1.0-8.75)], were lower in the LT patients compared to those observed in the NASH patients (P = 0.009). In contrast, the LT recipients and NASH patients had similar inflammatory and endothelial serum markers compared to the controls (pg/mL): lower IL-10 levels (32.3 and 32.3 vs 62.5, respectively, P = 0.019) and higher IFNγ (626.1 and 411.9 vs 67.9, respectively, P < 0.001), E-selectin (48.5 and 90.03 vs 35.7, respectively, P < 0.001), sVCAM-1 (1820.6 and 1692.4 vs 1167.2, respectively, P < 0.001), and sICAM-1 (230.3 and 259.7 vs 152.9, respectively, P = 0.015) levels. CONCLUSION: Non-obese LT recipients have similar pro-atherosclerotic serum profiles after a short 1-year follow-up period compared to NASH patients, suggesting a high risk of atherosclerosis in this population.