Uremic serum induces prothrombotic changes in venous endothelial cells and inflammatory changes in aortic endothelial cells.

BACKGROUND: Uremia induces various pathologic changes in the endothelium. However, there is limited information about the differences of these effects in endothelial cells originating from different parts of the vascular tree. METHODS: The effect of uremic serum obtained from patients with end stage renal failure on the gene expression and secretory activity of venous endothelial cells (VEC) and aortic endothelial cells (AEC) was studied in in vitro culture. RESULTS: In VEC, the expression of genes regulating the synthesis of von Willebrand factor (vWF) was increased by 254% (p<.005), vascular endothelial growth factor (VEGF) synthesis by 150% (p<.001), tissue plasminogen activator (t-PA) synthesis by 62% (p<.005), platelet endothelial cell adhesion molecule by 89% (p<.005), and the expression of gene regulating interleukin-6 (IL-6) synthesis was reduced. In AEC, the expression of the gene regulating synthesis of IL-6 was increased by 174% (p<.001), and the expression of the other genes was reduced. The secretion of IL-6 was reduced in VEC by 38% (p<.01) and increased in AEC by 55% (p<.005). In VEC, increased synthesis of VEGF 64% (p<.001) vWF (+34%, p<.01), and t-PA (+53%, p<.002) was observed, and in AEC it was reduced. CONCLUSIONS: VEC and AEC respond in different ways after exposure to uremic serum. VEC acquires the prothrombotic phenotype, whereas in AEC the inflammatory phenotype appears.

Protein-bounded uremic toxin p-cresylsulfate induces vascular permeability alternations.

The goal of the present studies is to investigate that the impact of p-cresylsulfate (PCS) on the endothelial barrier integrity via in situ exposure and systemic exposure. Vascular permeability changes induced by local injection of PCS were evaluated by the techniques of both Evans blue (EB) and India ink tracer. Rats were intravenously injected with EB or India ink followed by intradermal injections of various doses of PCS (0, 0.4, 2, 10 and 50 µmol/site) on rat back skins. At different time points, skin EB was extracted and quantified. The administration of India ink was used to demonstrate leaky microvessels. Skin PCS levels were also determined by liquid chromatography-mass spectrometry. We also investigated whether the increased endothelial leakage occurred in the aortic endothelium in rats treated with 5/6 nephrectomy and intraperitoneal injection of PCS 50 mg/kg/day for 4 weeks. The aortic endothelial integrity was evaluated by increased immunoglobulin G (IgG) leakage. High doses of PCS, but not lower doses, significantly induced vascular leakage as compared to saline injection and EB leakage exhibited in time-dependent manner. A time-correlated increase in leaky microvessels was detected in the tissues examined. The injected PCS declined with time and displayed an inverse relationship with vascular leakage. Chronic kidney disease (CKD) rats administered with PCS, compared to control rats, had significantly higher serum levels of PCS and apparent IgG deposition in the aortic intima. Increased endothelial leakage induced by PCS in skin microvessels and the aorta of CKD rats suggests that the PCS-induced endothelial barrier dysfunction.

Age-related changes in the expression of ICAM-1 in the aorta of Wistar albino rats / Cambios relacionados con la edad en la expresión de ICAM-1 en la aorta de ratas Wistar albinas

ICAM-1 which is expressed by endothelial cells and leukocytes are observed as first markers in diseases such as transplant rejection, diabetes and atherosclerosis and in infections caused by various pathogens. In the present study, it is aimed to reveal the age-related changes in the expression of ICAM-1 on rats. Therefore, a total of 30 albino rats were taken at the age of 6, 18 and 24 months without gender discrimination. Rats were fed with standard pellet feed during the study. Afterwards, rats were sacrificed and tissue samples were collected from their rats, and the samples were evaluated under the light microscope by staining with immnunohistochemical method. It was determined that the expression of both aortic endothelial cells and endothelial cells in the media layer had been significantly increased based on the age.

ICAM-1, que se expresa en las células endoteliales y los leucocitos, se observan como primeros marcadores de enfermedades como el rechazo de trasplante, la diabetes y la aterosclerosis y en las infecciones causadas por diversos patógenos. En el presente estudio, se pretende revelar los cambios relacionados con la edad en la expresión de ICAM-1 en ratas. Un total de 30 ratas albinas fueron seleccionadas con edades de 6, 18 y 24 meses, sin discriminación de sexo. Durante el estudio se administró a las ratas alimentación estándar de pellets. Posteriormente, los animales fueron sacrificados y se recogieron muestras de sus tejidos, los cuales fueron teñidos para inmunohistoquímica y se evaluaron a través de microscopio óptico. Se determinó que la expresión tanto de células endoteliales aórticas como de células endoteliales de la capa media se incrementó significativamente en función de la edad.

Rat Aortic Endothelium Damage Caused by Carbon Nanotubes Exposure / 环境与健康杂志

Objective To investigate the effect of nanotubes on rat aortic endothelium damage.Methods Wistar rats were intratracheally instilled with carbon nanotubes(CNTs) at the doses of 0,3.5 and 17.5 mg/kg,and with a carbon black negative control,or a quartz positive control.The rats were euthanized after 7 or 30 days of the single treatment,the oxidative stress(GSH,O_2~-?) was determined by using biochemical kits,the expression of sICAM-1 and sVCAM-1 in serum was determined by using ELISA kits and ICAM-1 and VCAM-1 on aortic endothelium was determined with immunohischemistry.Results The content of GSH and O_2~1?in serum increased with a dose-dependent and time-dependent manner.A up-regulated expression of sICAM-1 and sVCAM-1 in serum and ICAM-1 and VCAM-1 in the aortic endothelium was seen.No vascular damage was seen in the rat treated with carbon black,in those treated with high-dose CNTs obvious inflammation was revealed.Conclusion Carbon nanotubes exposure can induce oxidative stress which may be followed by the up-regulated expression of sICAM-1 and sVCAM-1 in serum and ICAM-1 and VCAM-1 in the aortic endothelium,and then the endothelium disfunction may occur.