ABSTRACT
En la década de los 90 se descubrió un nuevo sistema de comunicación célula-célula a través de vesículas con moléculas bioactivas liberadas al espacio extracelular. Estas vesículas, conocidas como vesículas extracelulares (VE), actúan como reguladores de procesos fisiológicos, pero también participan en el desarrollo y progresión de múltiples patologías. Las microvesículas (MVs) son un tipo de VE que se producen como resultado del daño celular, y están implicadas en la etiopatogenia de un gran número de enfermedades cardiovasculares porque intervienen en el inicio de la aterosclerosis. Diferentes fármacos cardioprotectores han demostrado tener un efecto sobre las MVs; por otro lado, desde que se conoce su capacidad para transferir información biológica, el uso de las éstas como vehículos de suministro molecular ha adquirido interés científico. El objetivo de este trabajo es analizar la implicación de las MVs en la etiopatogenia de la aterosclerosis estableciendo su importancia como biomarcadores de diagnóstico y de seguimiento. Se revisará el efecto farmacológico de las terapias actuales sobre las MVs y se discutirá su papel como herramienta terapéutica
In the 1990's, it was discovered a new cell-cell communication system based on the action of vesicles that cargo bioactive molecules, on neighboring cells. These vesicles, known as extracellular vesicles (EVs) act as regulators of several physiological processes but also participate in the development and progression of multiple diseases. Microvesicles (MVs) are types of EVs that are implicated in the etiopathogenesis of a large number of cardiovascular diseases due to they take part in the onset of atherosclerosis. Different cardioprotective drugs have shown to have an effect on MVs. In addition, since the discovery that MVs are capable of transferring biological information, the use of them as drug delivery vehicles has gained scientific interest. The aim of this work is to analyze the involvement of MVs in the origin of atherosclerosis to demonstrate their role as diagnostic biomarkers, as well as to review the pharmacological effect of current therapies on MVs and their role as therapeutic tool
Subject(s)
Humans , Drug Delivery Systems , Extracellular Vesicles , Platelet Aggregation Inhibitors/pharmacology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/drug therapy , Biomarkers, Pharmacological , Extracellular Vesicles/classificationABSTRACT
Coronary heart disease is associated with high morbidity and mortality. Endothelial dysfunction in affected patients is linked to long-term atherosclerotic disease progression and cardiovascular event rates. The present paper reports on changes in the levels of endothelial progenitor cells (VEGFR2/CD133/CD34), essential for endothelial repair, and of endothelial microvesicles (CD31/annexin V) as indicators of endothelial lesion, in patients undergoing coronary bypass surgery with respect both to baseline levels and to counts in healthy subjects. In an observational descriptive study, 31 patients scheduled for coronary revascularization surgery were compared with those of 25 healthy controls. In a subsequent longitudinal study, patients undergoing surgery were monitored at 5 timepoints up until 48 h after surgery. Endothelial progenitor cell (VEGFR2/CD133/CD34) and endothelial microvesicle (CD31/annexin V) levels were quantified by flow cytometry. Baseline endothelial progenitor cell counts in coronary patients were significantly lower than those of healthy controls (p < 0.001); however, after surgery, levels rose steadily over all 5 timepoints to 48 h with statistically significant differences (p < 0.001) between intra-operative and 48 h after surgery (T5). Endothelial microvesicle levels were significantly higher in coronary patients prior to surgery than in healthy controls (p < 0.001), and despite declining at 48 h remained significantly higher than those of controls (p < 0.001). Coronary surgery has had a positive impact on the endothelium in the patients, prompting a decrease in signs of endothelial dysfunction and a considerable improvement in the endothelial repair mechanisms involved in angiogenesis, playing an important role in the inflammatory response and the remodelling process of ischemic myocardium in postoperative period.
