Blunted transcriptional response to skeletal muscle ischemia in rats with chronic kidney disease: potential role for impaired ischemia-induced angiogenesis.

Abstract:

: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 killed 24 h 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, we analyzed RNA with Affymetrix GeneChip Rat Genome 230 2.0 Arrays. RT-PCR analysis of selected genes was performed to validate observed changes. Hindlimb ischemia upregulated 239 genes in CKD and 299 genes in control rats (66% overlap), whereas only a few genes were downregulated (14 in CKD and 34 in controls) compared with the nonischemic limb of the same animals. Comparison between the ischemic limbs of CKD and controls revealed downregulation 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 that may underlie the impaired postischemic angiogenesis in CKD.

journal_name

Physiol Genomics

journal_title

Physiological genomics

authors

Heiss RU,Fahlbusch FB,Jacobi J,Daniel C,Ekici AB,Cordasic N,Amann K,Hartner A,Hilgers KF

doi

10.1152/physiolgenomics.00124.2016

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

230-237

issue

4

eissn

1094-8341

issn

1531-2267

pii

physiolgenomics.00124.2016

journal_volume

49

pub_type

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