Daño a células endoteliales en cultivo inducido por el isoprostano 8-iso-PGF2a / Damage to cultured endothelial cells induced by isoprostane 8-iso PGF2

INTRODUCCIÓN: el endotelio vascular posee un papel esencial en los procesos asociados a la enfermedad cardiovascular. Existe estrecha relación entre el desbalance redox de estas células y la aparición y evolución de estas enfermedades. Entre los marcadores de daño oxidativo a los lípidos de membranas se encuentra el isoprostano 8-iso-PGF2a, que aumenta en estos pacientes. OBJETIVO: evaluar el efecto del isoprostano 8-iso-PGF2a sobre células endoteliales en cultivo y la protección con la proteína de estrés térmico a-cristalina. MÉTODOS: se cultivaron células endoteliales de la línea H5V y se evaluó el efecto del isoprostano 8-iso-PGF2a y del análogo del tromboxano A2, U46619, sobre la supervivencia celular. Se evaluó el efecto protector de la proteína de estrés térmico a-cristalina a través de la incubación de los cultivos con 1 mg/ml de la proteína previo a la inducción del daño con los compuestos en estudio. RESULTADOS: la supervivencia celular disminuyó proporcional al aumento de la concentración del isoprostano y del U46619. La a-cristalina aumentó la supervivencia celular en un 20 % al preincubar los cultivos sometidos al efecto de ambos compuestos. CONCLUSIONES: el isoprostano 8-iso-PGF2a, además, de ser un marcador de daño oxidativo puede ser considerado un inductor directo de daño a las células del endotelio vascular, efecto mediado a través, de la generación de tromboxano A2 o la activación de su receptor. La proteína de estrés térmico a-cristalina, añadida de forma exógena, puede considerarse un protector endotelial.

INTRODUCTION: the vascular endothelium plays an essential role in processes associated with cardiovascular disease. There is a close relationship between redox imbalance in these cells and the appearance and evolution of such diseases. Increased isoprostane 8-iso PGF2 is among the markers of oxidative damage to membrane lipids in these patients. OBJECTIVE: evaluate the effect of isoprostane 8-iso PGF2 on cultured endothelial cells and the protection provided by -crystallin heat-shock stress protein. METHODS: endothelial cells from line H5V were cultured to evaluate the effect of isoprostane 8-iso PGF2 and thromboxane A2 analog U46619 on cell survival. An evaluation was conducted of the protective effect of -crystallin heat-shock stress protein by incubation of the cultures with 1 mg/ml of the protein prior to damage induction with the study compounds. RESULTS: cell survival decreased as isoprostane and U46619 concentration increased. -Crystallin increased cell survival by 20% upon preincubation of the cultures subjected to both compounds. CONCLUSIONS: besides being an oxidative damage marker, isoprostane 8-iso PGF2 may be considered a direct inducer of damage to vascular endothelial cells. This effect is mediated by the generation of thromboxane A2 or the activation of its receptor. Added exogenously, -crystallin heat-shock stress protein may be considered to be an endothelial protector.

Interrelación del equilibrio tromboxano A2-prostaciclina y su modificación cuando se ingiere aspirina / Interrelation of the balance tromboxano A2-prostaciclina and its modification when aspirin is ingested

Introducción: la aspirina, es usada por su acción antiinflamatoria, analgésica, antipirética y antiagregante plaquetaria. El conocimiento del metabolismo del ácido araquidónico es fundamental para el estomatólogo que basa su trabajo en diagnosticar y tratar procesos inflamatorios en tejidos bucodentales, también por su condición de cirujano debe estar alerta en no realizar intervenciones quirúrgicas en pacientes que estén tomando aspirina, por interrumpir este medicamento la agregación plaquetaria, importante paso de la hemostasia normal. Objetivo: interpretar la interrelación hemostática del tromboxano A2 y la prostaciclina en condiciones fisiológicas, y el resultado de su modificación cuando se ingiere aspirina. Método: PubMed fue empleada como fundamental fuente de búsqueda, que incluyó el conocimiento sobre el fármaco aspirina, la interacción del tromboxano y la prostaclina, y la acción que sobre el equilibrio de estos productos ejerce la aspirina; también se revisaron HINARI, LILACS y Medline. Desarrollo: el ácido araquidónico es un ácido graso poliinsaturado de 20 átomos de carbono (ácido 5, 8, 11, 14-eicosatetraenoico) que procede directamente de la dieta. La relación recíproca entre PG-I2 y el TxA2 constituye un mecanismo finamente equilibrado que sirve para regular la función plaquetaria del ser humano. La utilidad de la aspirina en los pacientes expuestos a trombogénesis se debe, en gran parte, a su capacidad para inhibir la síntesis del TxA2, agente derivado del ácido araquidónico, elemento que se encuentra esterificado a los fosfolípidos de la membrana plaquetaria. El óxido nítrico, igual que la PG-I2, actúa también como vasodilatador e inhibidor de la agregación plaquetaria. Conclusiones: los pacientes que acuden al estomatólogo y por prescripción facultativa están tomando aspirina, tienen su sistema plaquetario inhibido y no pueden sintetizar tromboxano. El proceder quirúrgico por parte del estomatólogo en un paciente que esté ingiriendo aspirina lo expone al desarrollo de hemorragia de causa iatrogénica(AU)

Introduction: aspirin is used by its arachidonic acid is fundamental for the dentist that bases its work on diagnosis and treatment of inflammatory processes, also for its surgeon condition he should be alert to do not carry out surgical interventions in patients that are taking aspirin, because this drug interrupts platelet aggregation, important step of the normal hemostasis. Objective: to interpret the hemostatic interrelation of the tromboxano A2 and the prostaciclina in physiologic conditions and the result of their modification when aspirin is ingested. Method: it was employee as fundamental search source the PubMed, other databases also revised they were HINARI, LILACS, Medline. Was carried out a search that included the knowledge on the drug aspirin, the interaction of the tromboxano and the prostaclina, and the action that it has more than enough the balance of these products it exercises the aspirin. Development: the arachidonic acid is a polyunsaturated fatty acid of 20 atoms of carbon (5, 8, 11, 14-eicosatetraenoic acid) that proceeds directly from diet. The reciprocal relationship between PG-I2 and TxA2 constitutes a finely balanced mechanism that is good to regulate the human being's platelet function. The utility of aspirin in patients exposed to thrombogenesis is largely due to its capacity to inhibit the synthesis of the TxA2, agent derived from arachidonic acid, which is esterified to the phospholipids of the platelet membrane. Nitric oxide, the same as the PG-I 2, also acts as vasodilator and inhibitor of the platelet aggregation. Conclusions: the patients that go to the dentist and for medical prescription are taking aspirin, have their platelet system inhibited and cannot synthesize tromboxane. Surgical processes performed by the dentist in a patient that is ingesting aspirin exposes him to the development of hemorrhage of yatrogenic cause(AU)

Thromboxane A2 modulates migration, proliferation, and differentiation of adipose tissue-derived mesenchymal stem cells

Prostanoid metabolites are key mediators in inflammatory responses, and accumulating evidence suggests that mesenchymal stem cells (MSCs) can be recruited to injured or inflamed tissues. In the present study, we investigated whether prostanoid metabolites can regulate migration, proliferation, and differentiation potentials of MSCs. We demonstrated herein that the stable thromboxane A2 (TxA2) mimetic U46619 strongly stimulated migration and proliferation of human adipose tissue-derived MSCs (hADSCs). Furthermore, U46619 treatment increased expression of alpha-smooth muscle actin (alpha-SMA), a smooth muscle marker, in hADSCs, suggesting differentiation of hADSCs into smooth muscle-like cells. U46619 activated ERK and p38 MAPK, and pretreatment of the cells with the MEK inhibitor U0126 or the p38 MAPK inhibitor SB202190 abrogated the U46619-induced migration, proliferation, and alpha-SMA expression. These results suggest that TxA2 plays a key role in the migration, proliferation, and differentiation of hADSCs into smooth muscle-like cells through signaling mechanisms involving ERK and p38 MAPK.

Effects of cyclo-oxygenase and thromboxane synthetase inhibitors on right atrial prostaglandins.

OBJECTIVES: The aim of this study was to find out the effects of cyclo-oxygenase and thromboxane synthetase inhibitors on right atrial prostacyclin and thromboxane A2 levels. METHODS: The study consisted of a total of 50 patients subjected to coronary bypass surgery. These patients were divided into two groups, Group I and Group II each consisting of 25 patients. In Group I patients, the right atrial tissues were studied for effects of indomethacin and U63557A on the prostaglandin levels. In Group II patients, the right atrial tissues were studied for effects of Aspirin and U63557A on the prostaglandin levels. RESULTS: In Group I patients, the atrial tissues pretreated with indomethacin showed a fall in the levels of 6 keto PGF1 alpha from 153.5 +/- 28.4 pg/0.1 mg to 59.7 +/- 11.6 pg/0.1 mg and of TXB2 from 41.6 +/- 1.2 pg/0.1 mg to 17.2 +/- 3.2 pg/0.1 mg. In the atrial tissues of Group I treated with U63557A the levels of 6 keto PGF1 alpha fell to 145.4 +/- 26.8 pg/0.1 mg and the levels of TXB2 fell to 14.7 +/- 2.8 pg/0.1 mg. In Group II patients, the atrial tissues pretreated with aspirin, showed a fall in the levels of 6 keto PGF1 alpha from 142.1 +/- 2.8 pg/0.1 mg to 17.5 +/- 0.8 pg/0.1 mg. In the atrial tissues pretreated with U63557A, the levels of 6 keto PGF1 alpha fell to 131.2 +/- 2.9 pg/0.1 mg and the levels of TXB2 fell to 14.4 +/- 0.7 pg/0.1 mg. CONCLUSIONS: The study showed that human right atrial tissues are capable of producing TXA2 in addition to prostacyclin. Indomethacin and aspirin by inhibiting generation of cyclic endoperoxides inhibited synthesis of both prostacyclin and TXA2. In contrast a thromboxane synthethase inhibitor U63557A selectively inhibited TXA2 without significant effects on prostacyclin synthesis.