The diversity and coexistence of extracellular mitochondria in circulation: A friend or foe of the immune system.

The diversity and coexistence of extracellular mitochondria may have a key role in the maintenance of health and progression of disease. Studies report that active mitochondria can be found physiologically outside of cells and circulating in the blood without inducing an inflammatory response. In addition, inactive or harmed mitochondria have been recognized as activators of immune cells, as they play an essential role in diseases characterized by the metabolic deregulation of these cells, such as sepsis. In this review we analyze key aspects regarding the existence of a diversity of extracellular mitochondria, their coexistence in body fluids and their effects on various immune cells. Additionally, we introduce models of how extracellular mitochondria could be interacting to maintain health and affect disease prognosis. Unwrapped mitochondria (freeMitos) can exist as viable, active, inactive or harmed organelles. Mitochondria can also be found wrapped in a membrane (wrappedMitos) that may differ depending on the cell of origin. Mitochondrial fragments can also be present in various body fluids as DAMPs, as mtDNA enclosed in vesicles or as circulating-cell-free mtDNA (ccf-mtDNA). Interestingly, the great quantity of evidence regarding the levels of ccf-mtDNA and their correlation with aging and disease allows for the identification of the diversity, but not type, of extracellular mitochondria. The existence of a diversity of mitochondria and their effects on immune cells opens a new concept in the biomedical field towards the understanding of health, the progression of disease and the development of mitochondria as therapeutic agents.

Glicocálix endotelial: relevancia clínica y enfoque traslacional / Endothelial glycocalyx: clinical relevance and translational approach

El glicocálix endotelial es una estructura sin forma definida que recubre la capa luminal del endotelio vascular y que está constituido, principalmente, por tres elementos: proteoglicanos, glucosaminoglicanos y glicoproteínas. Cumple distintas funciones, como regular la permeabilidad vascular a las moléculas y líquidos, la transducción de las fuerzas mecánicas de tensión y las cascadas de fibrinólisis y coagulación vascular; además, protege de la adhesión leucocitaria, plaquetaria y de patógenos. Los determinantes de lesión del glicocálix pueden ser de varios tipos, por ejemplo, incremento las fuerzas de tensión, especies reactivas de oxígeno (O2), aumento, a nivel plasmático, de sustancias como el sodio (hipernatremia), glucosa (hiperglicemia) y colesterol (hipercolesterolemia), y las moléculas proinflamatorias. Cualquiera de las noxas citadas, individualmente o combinadas, lesionan el glicocálix y la disfunción resultante se expresará clínicamente como disfunción endotelial, aumento de la permeabilidad vascular, paso de lipoproteínas al subendotelio, activación de la coagulación o aumento de la adhesión de plaquetas y leucocitos al endotelio.

Endothelial glycocalyx is an undefined structure covering the luminal layer of the vascular endothelium and consisting mainly of three elements: proteoglycans, glycosaminoglycans and glycoproteins. It has different functions, such as the regulation of vascular permeability to liquids and molecules; transduction of the mechanical forces of vascular tension; regulation of coagulation and fibrinolysis cascades; and protection of leukocyte, platelet and pathogen adhesion. The determinants of a glycocalyx lesion can be of several types­e.g., increased tensile forces; reactive oxygen (O2) species; increased plasma level of substances such as sodium (hypernatremia), glucose (hyperglycemia) and cholesterol (hypercholesterolemia); and pro-inflammatory molecules. Any of the above-mentioned noxas, alone or combined, injure the glycocalyx. Its dysfunction will be clinically expressed as endothelial dysfunction, increased vascular permeability, filtration of lipoproteins to the subendothelium, activation of coagulation, or increased adhesion of leukocytes and platelets to the endothelium.