Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Previous studies indicated an impairment of ischemia-induced angiogenesis in skeletal muscle of rats with CKD. We performed a systematic comparison of early gene expression in response to ischemia in rats with or without CKD to identify potential molecular mechanisms underlying impaired angiogenesis in CKD. CKD was induced in male rats by 5/6 nephrectomy (SNX); control rats were sham operated (sham). Eight weeks later, ischemia of the right limb was induced by ligation and resection of the femoral artery. Rats were sacrificed 24 hours after the onset of ischemia, and RNA was extracted from the musculus soleus of the ischemic and the nonischemic hindlimb. To identify differentially expressed transcripts, RNA was analyzed employing Affymetrix GeneChip Rat Genome 230 2.0 Arrays. RT-PCR analysis of selected genes was performed to validate observed changes. Hindlimb ischemia up-regulated 239 genes in CKD and 299 genes in control rats (66% overlap) whereas only a few genes were down-regulated (14 in CKD and 34 in controls), compared with the non-ischemic limb of the same animals. Comparison between the ischemic limbs of CKD and controls revealed down-regulation of 65 genes in CKD; 37 of these genes were also among the ischemia-induced genes in controls. Analysis of functional groups (other than angiogenesis) pointed to genes involved in leukocyte recruitment and fatty acid metabolism. Transcript expression profiling points to a relatively small number of differentially expressed genes which may underlie the impaired post-ischemic angiogenesis in CKD.
- chronic kidney disease
- skeletal muscle
- Copyright © 2016, Physiological Genomics