Abstract 11343: High Density Lipoprotein (HDL) From Patients with Early Kidney Disease (CKD) Exerts Adverse Endothelial Effects
Background Patients with chronic kidney disease (CKD) have a particularly high cardiovascular morbidity and mortality. High-density lipoprotein (HDL) from healthy subjects has been observed to exert endothelial-protective effects, however, the vascular effects of HDL can be highly heterogenous. We have therefore examined endothelial effects of HDL isolated from patients with different stages of CKD and healthy subjects.
Methods HDL was isolated from patients with CKD (K/DOQI stadium II, IV, V, each n=15) and healthy subjects (HS; n=15) by sequential ultracentrifugation. The effect of HDL on endothelial nitric oxide production (NO) was assessed by electron spin resonance (ESR) spectroscopy. The anti-inflammatory capacity of HDL was examined as well as the endothelial anti-apoptotic effects of HDL. In vitro as well as in vivo endothelial repair capacity of HDL were examined using a carotid injury model in nude mice.
Results HDL from healthy subjects stimulated endothelial cell NO production; in marked contrast HDL from CKD patients substantially inhibited endothelial NO production (-80.5 % HDL-CKD vs. HDL-HS; P<0.01). HDL from healthy subjects attenuated endothelial VCAM-1 expression, whereas HDL from patients with CKD induced basal endothelial VCAM-1 expression. Furthermore, HDL from healthy subjects, but not HDL from patients with CKD significantly reduced endothelial cell apoptosis (number of Annexin V+/PI- cells after treatment with TNFα), indicating a loss of HDL's endothelial antiapoptotic capacity in CKD. In vitro gap closure and in vivo reendothelialization after carotid injury were markedly suppressed by HDL of CKD patients of all stages.
Conclusion Our data demonstrate for the first time that important endothelial-protective effects of HDL, such as stimulation of endothelial NO production and promotion of endothelial repair, are substantially altered in patients with CKD, already in the early stages of the disease. These findings reveal a novel potentially important pathomechanism of accelerated cardiovascular disease in patients with CKD.
- © 2011 by American Heart Association, Inc.