Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease

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  • Jane Stubbe, From the Department of Biochemistry and Pharmacology, Odense University Hospital (S.A.R.P., L.P.K., H.C.B., P.S.J., M.B.-P., M.L.H., L.M.R.) and Protein Research Group, Department of Biochemistry and Molecular Biology (M.R.L.), University of Southern Denmark, Odense, Denmark; Center for Individualized Medicine in Arterial Diseases (CIMA), Center for Clinical Proteomics (CCP), Odense Patient Explorative Network (OPEN) (S.A.R.P., L.P.K., H.C.B., P.S.J., M.B.-P., M.L.H., L.M.R.) and Department of Cardiothoracic and Vascular Surgery (M.L.H.), Odense University Hospital, Odense, Denmark; and Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark (P.S.N., T.S.).
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  • Vibe Skov, Department of Hematology, Roskilde Hospital, Zealand University Hospital, Sygehusvej 10, DK-4000 Roskilde, Denmark.
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  • Helle Charlotte Thiesson, Department of Nephrology, Odense University Hospital, Odense, Denmark.
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  • Karl Egon Larsen, Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark
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  • Maria Lyck Hansen
  • Boye L Jensen, Cardiovascular and Renal Research Unit, Institute of Molecular Medicine, University of Southern Denmark , Odense , Denmark.
  • ,
  • Bente Jespersen
  • Lars Melholt Rasmussen, From the Department of Biochemistry and Pharmacology, Odense University Hospital (S.A.R.P., L.P.K., H.C.B., P.S.J., M.B.-P., M.L.H., L.M.R.) and Protein Research Group, Department of Biochemistry and Molecular Biology (M.R.L.), University of Southern Denmark, Odense, Denmark; Center for Individualized Medicine in Arterial Diseases (CIMA), Center for Clinical Proteomics (CCP), Odense Patient Explorative Network (OPEN) (S.A.R.P., L.P.K., H.C.B., P.S.J., M.B.-P., M.L.H., L.M.R.) and Department of Cardiothoracic and Vascular Surgery (M.L.H.), Odense University Hospital, Odense, Denmark; and Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark (P.S.N., T.S.).

Uremia accelerates atherosclerosis, but little is known about affected pathways in human vasculature. This study aimed to identify differentially expressed arterial transcripts in patients with chronic kidney disease (CKD). Global mRNA expression was estimated by microarray hybridization in iliac arteries ( n = 14) from renal transplant recipients and compared with renal arteries from healthy living kidney donors ( n = 19) in study 1. Study 2 compared nonatherosclerotic internal mammary arteries (IMA) from five patients with elevated plasma creatinine levels and age- and sex-matched controls with normal creatinine levels. Western blotting and immunohistochemistry for selected proteins were performed on a subset of study 1 samples. Fifteen gene transcripts were significantly different between the two groups in study 1 [fold changes (FC) > 1.05 and false discovery rates (FDR) < 0.005]. Most upregulated mRNAs associated with cellular signaling, apoptosis, TNFα/NF-κB signaling, smooth muscle contraction, and 10 other pathways were significantly affected. To focus attention on genes from genuine vascular cells, which dominate in IMA, concordant deregulated genes in studies 1 and 2 were examined and included 23 downregulated and eight upregulated transcripts (settings in study 1: FC > 1.05 and FDR < 0.05; study 2: FC > 1.2 and P < 0.2). Selected deregulated gene products were investigated at the protein level, and whereas HIF3α confirmed mRNA upregulation, vimentin showed upregulation in contrast to the mRNA results. We conclude that arteries from CKD patients display change in relatively few sets of genes. Many were related to differentiated vascular smooth muscle cell phenotype. These identified genes may contribute to understanding the development of arterial injury among patients with CKD.

Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Volume314
Issue6
Pages (from-to)F1117-F1128
ISSN1931-857X
DOIs
Publication statusPublished - 13 Jun 2018

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