RESUMO
An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.
Assuntos
Angina Pectoris/fisiopatologia , Isquemia Encefálica/fisiopatologia , Cloreto de Cálcio/sangue , Doença da Artéria Coronariana/fisiopatologia , Células Endoteliais/patologia , Infarto do Miocárdio/fisiopatologia , Fosfatos/sangue , Angina Pectoris/sangue , Angina Pectoris/genética , Animais , Aorta/metabolismo , Aorta/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Cloreto de Cálcio/química , Estudos de Casos e Controles , Morte Celular , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal , Floculação , Regulação da Expressão Gênica , Humanos , Inflamação , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Leucócitos/metabolismo , Leucócitos/patologia , Lisossomos/metabolismo , Lisossomos/patologia , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Fosfatos/química , Cultura Primária de Células , Ratos , Ratos Wistar , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Quick label-free virus screening and highly sensitive analytical tools/techniques are becoming extremely important in a pandemic. In this study, we developed a biosensing device based on the silicon nanoribbon multichannel and dielectrophoretic controlled sensors functionalized with SARS-CoV-2 spike antibodies for the use as a platform for the detection and studding of properties of viruses and their protein components. Replicatively defective viral particles based on vesicular stomatitis viruses and HIV-1 were used as carrier molecules to deliver the target SARS-CoV-2 spike S-proteins to sensory elements. It was shown that fully CMOS-compatible nanoribbon sensors have the subattomolar sensitivity and dynamic range of 4 orders. Specific interaction between S-proteins and antibodies leads to the accumulation of the negative charge on the sensor surface. Nonspecific interactions of the viral particles lead to the positive charge accumulation. It was shown that dielectrophoretic controlled sensors allow to estimate the effective charge of the single virus at the sensor surface and separate it from the charge associated with the binding of target proteins with the sensor surface.