RESUMO
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.
Assuntos
Biomarcadores , COVID-19 , Trombomodulina , Ativador de Plasminogênio Tipo Uroquinase , Fator de von Willebrand , Humanos , COVID-19/mortalidade , COVID-19/sangue , Masculino , Fator de von Willebrand/metabolismo , Fator de von Willebrand/análise , Pessoa de Meia-Idade , Feminino , Biomarcadores/sangue , Idoso , Ativador de Plasminogênio Tipo Uroquinase/sangue , Trombomodulina/sangue , Estudos Prospectivos , Prognóstico , SARS-CoV-2 , Adulto , Endotélio Vascular/fisiopatologia , Mortalidade Hospitalar , Modelos de Riscos ProporcionaisRESUMO
We examined the activity of the serine protease urokinase-type plasminogen activator (uPA) present in the euglobulin fraction of plasma from 17 demented patients with probable Alzheimer's disease (AD), 12 patients with vascular dementia (VD) and 10 healthy controls. Euglobulin protein fractions were separated by electrophoresis and gels were incubated at the surface of plasminogen-rich casein-agarose underlays. The degradative activity of uPA in this system was measured by densitometric analysis. In 8/17 (47%) patients with AD we observed an excessive uPA activity (> 200 mIU/ml). In contrast, only 2/12 (16%) patients with VD and 1/10 (10%) control subjects revealed a comparable increase in circulating uPA activity. Further evaluation of dementia stage in patients with AD allow us to associate high levels of uPA activity with severity of disease. uPA levels were significantly elevated (2.8-fold increase) in AD patients with severe cognitive and memory impairments (Alzheimer Disease Assessment Scale) with respect to controls, VD patients or AD patients with moderate cognitive and memory impairments (P < 0.001, ANOVA). Our data suggest that the anormalities in circulating fibrinolytic enzymes could be correlated with the severity of dementia. In light of this findings, the free uPA activity in euglobulin plasma fraction should be considered a marker of serious damage in patients with AD.
Assuntos
Doença de Alzheimer/sangue , Soroglobulinas/análise , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/enzimologia , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Ativador de Plasminogênio Tipo Uroquinase/sangueRESUMO
The fibrinolytic activity present in the euglobulin (EU) fraction of BALB/c mice before and during the growth of M3 and MM3 murine mammary adenocarcinomas was characterized. The main plasminogen activator (PA) form contained in EUs from control mice was defined as murine urokinase-type PA (uPA). Overall fibrinolytic activity decreased significantly during tumor development. Zymographies showed that this fall was associated with a reduction in the free uPA band (47 kDa) and to the detection of a tissue-type PA (tPA) complexed band (117 kDa). Western blotting showed free tPA protein (68 kDa) in control mice, that disappeared in M3 tumor-bearing mice. In this model, high subcutaneous tumor burden induces a severe impairment in the circulating fibrinolytic system.