RESUMO
La enfermedad del hígado graso no alcohólico (EHGNA) es la enfermedad hepática crónica más común del mundo. La EHGNA se considera la manifestación hepática del síndrome metabólico al estar directamente asociada con la obesidad, la resistencia a la insulina, la diabetes mellitus tipo 2 y las complicaciones cardiovasculares. Pese a su prevalencia, los factores que desencadenan la progresión de la EHGNA a la esteatohepatitis no alcohólica, la cirrosis y el carcinoma hepatocelular son poco conocidos. Actualmente, no existe tratamiento eficaz ni hay disponible un método fiable para su diagnóstico y estatificación más allá de la biopsia hepática altamente invasiva.Recientemente, las vesículas extracelulares (VEs) han emergido como posibles biomarcadores para el diagnóstico de la EHGNA. Las VEs son vesículas derivadas de las células que contienen proteínas y ácidos nucleicos, entre otros componentes, que interactúan y desencadenan una gran variedad de respuestas en células diana próximas o distantes. Varios mecanismos implicados en la progresión de la EHGNA, como la inflamación, la fibrosis y la angiogénesis, relacionados con la lipotoxicidad, desencadenan la secreción de VEs por las células hepáticas. En esta revisión nos centraremos en las VEs secretadas por los hepatocitos (Hep-VEs) como mensajeros del interactoma entre las diferentes células hepáticas en la patogénesis de la EHGNA, así como en su papel como biomarcadores no invasivos para su diagnóstico y estratificación. Además, destacaremos las investigaciones disponibles hasta la fecha, las limitaciones actuales y las futuras directrices para su implementación en un entorno clínico como biomarcadores o dianas terapéuticas de la enfermedad hepática. (AU)
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD, the hepatic manifestation of the metabolic syndrome, closely associates with insulin resistance, type 2 diabetes mellitus, obesity and cardiovascular disease. Until now, the specific factors involved in the progression of NAFLD from fatty liver to non-alcoholic steatohepatitis, cirrhosis and, ultimately hepatocellular carcinoma have not been totally elucidated.Also, patients have to face the lack of efficient or personalized treatments, as well as the absence of reliable diagnosis or staging methods beyond the highly invasive liver biopsy. In the last years, extracellular vesicles (VEs) are considered as potential biomarkers for the diagnosis many diseases including NAFLD. VEs are released by different cells types into the circulation and contain nucleic acids and proteins, among other components of their, that interact with surrounding or distant target cells, thereby triggering a plethora of responses. During NAFLD progression, several processes such as inflammation, fibrosis and angiogenesis, all related to MS-associated lipotoxicity, lead to VEs release by liver cells. In this review we will focus in the role of hepatocyte-derived VEs (Hep-VEs) and their interactions with non-parenchymal liver cells populations during NAFLD pathogenesis, as well as in their role as non-invasive biomarkers for disease diagnosis and progression. We will highlight the recent work currently available on VEs in the context of NAFLD, the current limitations and future directions for the implementation of VEs as biomarkers or targets of liver disease in the clinical setting. (AU)
Assuntos
Hepatócitos , Inflamação , Vesículas Extracelulares , BiomarcadoresRESUMO
La enfermedad del hígado graso no alcohólico (EHGNA) es la enfermedad hepática crónica más común del mundo. La EHGNA se considera la manifestación hepática del síndrome metabólico al estar directamente asociada con la obesidad, la resistencia a la insulina, la diabetes mellitus tipo 2 y las complicaciones cardiovasculares. Pese a su prevalencia, los factores que desencadenan la progresión de la EHGNA a la esteatohepatitis no alcohólica, la cirrosis y el carcinoma hepatocelular son poco conocidos. Actualmente, no existe tratamiento eficaz ni hay disponible un método fiable para su diagnóstico y estatificación más allá de la biopsia hepática altamente invasiva.Recientemente, las vesículas extracelulares (VEs) han emergido como posibles biomarcadores para el diagnóstico de la EHGNA. Las VEs son vesículas derivadas de las células que contienen proteínas y ácidos nucleicos, entre otros componentes, que interactúan y desencadenan una gran variedad de respuestas en células diana próximas o distantes. Varios mecanismos implicados en la progresión de la EHGNA, como la inflamación, la fibrosis y la angiogénesis, relacionados con la lipotoxicidad, desencadenan la secreción de VEs por las células hepáticas. En esta revisión nos centraremos en las VEs secretadas por los hepatocitos (Hep-VEs) como mensajeros del interactoma entre las diferentes células hepáticas en la patogénesis de la EHGNA, así como en su papel como biomarcadores no invasivos para su diagnóstico y estratificación. Además, destacaremos las investigaciones disponibles hasta la fecha, las limitaciones actuales y las futuras directrices para su implementación en un entorno clínico como biomarcadores o dianas terapéuticas de la enfermedad hepática. (AU)
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD, the hepatic manifestation of the metabolic syndrome, closely associates with insulin resistance, type 2 diabetes mellitus, obesity and cardiovascular disease. Until now, the specific factors involved in the progression of NAFLD from fatty liver to non-alcoholic steatohepatitis, cirrhosis and, ultimately hepatocellular carcinoma have not been totally elucidated.Also, patients have to face the lack of efficient or personalized treatments, as well as the absence of reliable diagnosis or staging methods beyond the highly invasive liver biopsy. In the last years, extracellular vesicles (VEs) are considered as potential biomarkers for the diagnosis many diseases including NAFLD. VEs are released by different cells types into the circulation and contain nucleic acids and proteins, among other components of their, that interact with surrounding or distant target cells, thereby triggering a plethora of responses. During NAFLD progression, several processes such as inflammation, fibrosis and angiogenesis, all related to MS-associated lipotoxicity, lead to VEs release by liver cells. In this review we will focus in the role of hepatocyte-derived VEs (Hep-VEs) and their interactions with non-parenchymal liver cells populations during NAFLD pathogenesis, as well as in their role as non-invasive biomarkers for disease diagnosis and progression. We will highlight the recent work currently available on VEs in the context of NAFLD, the current limitations and future directions for the implementation of VEs as biomarkers or targets of liver disease in the clinical setting. (AU)
Assuntos
Humanos , Fígado Gorduroso , Inflamação , Vesículas Extracelulares , Biomarcadores , Carcinoma Hepatocelular , Insulina , Diabetes Mellitus Tipo 2RESUMO
@#The role of extracellular vesicles (EV) in osteoarthritis has become the focus of much research. These vesicles were isolated from several cell types found in synovial joint including chondrocytes and synovium. As articular cartilage is an avascular tissue surrounded by synovial fluid, it is believed that EV might play a crucial role in the homeostasis of cartilage and also could hold key information in the pathogenesis of osteoarthritis. This is thought to be due to activation of pro-inflammatory factors leading to a catabolic state and degradation of cartilage. In addition, due to the nature of articular cartilage lacking neuronal innervation, knowledge of EV can contribute to identification of novel biomarkers in this debilitating condition. This can be either directly isolated from aspirate of synovial fluid or from peripheral blood. Finally, EVs are known to shuttle important signalling molecules which can be utilised as unique modality in transferring therapeutic compounds in a cell free manner.
