title: 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.
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.|Department of Radiology, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.
authors.forename: Rafael U
authors.initials: RU
authors.lastname: Heiss
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.
authors.forename: Fabian B
authors.initials: FB
authors.lastname: Fahlbusch
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Jacobi
authors.affiliation: Institute for Nephropathology, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.
authors.forename: Nada
authors.initials: N
authors.lastname: Cordasic
authors.affiliation: Institute for Nephropathology, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany; and.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander University, Erlangen-Nuremberg (FAU), Germany; Karl.Hilgers@uk-erlangen.de.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007511:Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
keywords: angiogenesis; chronic kidney disease; ischemia; microarray; skeletal muscle