Prostacyclin synthesis in irradiated endothelial cells cultured from bovine aorta

Abstract

Confluent monolayers of bovine aortic endothelial cells were examined 2-72 h after exposure to 0.5-5.0 Gy of 60Co gamma-rays. Accumulation of prostacyclin [PGI2, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] in the culture media and PGI2 production stimulated by exogenous arachidonate were correlated with cell detachment and release of lactate dehydrogenase (LDH) activity. Platelet adherence to irradiated and control monolayers also was studied. There were simultaneous time- and dose-dependent increases in cell detachment and in the titers of 6-keto-PGF1 alpha and LDH activity in the culture medium. These changes were evident between 4 and 8 h after 5 Gy or at 24 h after 0.5 Gy. Four hours after 5 Gy, both adherent and detached endothelial cells showed a twofold increase in PGI2 production during a 15-min incubation with arachidonate (10 microM). However, by 72 h this increase was less significant. The accumulation of 6-keto-PGF1 alpha appeared to be related to cell destruction, but radiation also stimulated PGI2 synthesis independent of cell detachment. There was an increased platelet interaction with irradiated monolayers, as a result of platelet adherence to subendothelial matrix exposed after cell detachment. However, irradiation did not alter the nonadherent property of the endothelial cell surface toward platelets.

Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

“…In the acute phase, radiation increases endothelial cell permeability and expression of chemokines and adhesion molecules, and causes loss of vascular thromboresistance (3,4). Radiation-induced loss of vascular thromboresistance is a result of decreased fibrinolytic activity (24), increased expression of tissue factor (TF) (25,26) and von Willebrand factor (27), and decreased expression of prostacyclin (28) and TM (5,(29)(30)(31). TM is a transmembrane glycoprotein, located on the luminal surface of endothelial cells in most normal blood vessels.…”

Hirudin ameliorates intestinal radiation toxicity in the rat: support for thrombin inhibition as strategy to minimize side‐effects after radiation therapy and as countermeasure against radiation exposure

“…The vascular endothelium is a major target for ionizing radiation. Acutely, radiation causes endothelial cell apoptosis, increases endothelial permeability, induces the expression of chemokines and adhesion molecules, and decreases vascular thromboresistance by increasing the expression of TF [14] and von Willebrand factor (VWF) [15] and decreasing the expression of prostacyclin [16] and thrombomodulin [17].…”

Influence of radiographic contrast media on the secretion of vasoactive substances by primary human umbilical venous endothelial cells (HUVEC): Prospective, controlled, in vitro comparative study

“…shear, mechanical damage, radiation, cytotoxins, endotoxins, cyclosporine, arachidonic acid, etc. [5,15,[17][18][19][20]23]. Though morphological damage of human endothelial cells on extracellular matrices in vitro through radiographic contrast media has pre-viously been shown [6], biochemical evidence has been lacking.…”