Department of Biology, University of Patras, Patras, Achaia, Greece.
PLoS One. 2012;7(2):e30975. doi: 10.1371/journal.pone.0030975. Epub 2012 Feb 22.
Chronic kidney disease is linked to systemic inflammation and to an increased risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction associates with hypertension and vascular disease in the presence of chronic kidney disease but the mechanisms that regulate the activation of the endothelium at the early stages of the disease, before systemic inflammation is established remain obscure. In the present study we investigated the effect of serum derived from patients with chronic kidney disease either before or after hemodialysis on the activation of human endothelial cells in vitro, as an attempt to define the overall effect of uremic toxins at the early stages of endothelial dysfunction. Our results argue that uremic toxins alter the biological actions of endothelial cells and the remodelling of the extracellular matrix before signs of systemic inflammatory responses are observed. This study further elucidates the early events of endothelial dysfunction during toxic uremia conditions allowing more complete understanding of the molecular events as well as their sequence during progressive renal failure.
慢性肾脏病与全身炎症以及缺血性心脏病和动脉粥样硬化的风险增加有关。内皮功能障碍与高血压和慢性肾脏病存在时的血管疾病相关,但在全身炎症确立之前,调节疾病早期内皮细胞激活的机制仍不清楚。在本研究中,我们研究了慢性肾脏病患者在血液透析前后的血清对人内皮细胞体外激活的影响,试图定义在内皮功能障碍的早期阶段尿毒症毒素的整体作用。我们的结果表明,尿毒症毒素改变了内皮细胞的生物学作用,以及细胞外基质的重塑,而在观察到全身炎症反应的迹象之前。这项研究进一步阐明了毒血症条件下内皮功能障碍的早期事件,从而更全面地了解分子事件及其在进行性肾衰竭过程中的顺序。