Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease
| Autor: | Helle C. Thiesson, Karl Egon Larsen, Lars Melholt Rasmussen, Boye L. Jensen, Bente Jespersen, Vibe Skov, Maria Lyck Hansen, Jane Stubbe |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Vascular smooth muscle Physiology Blotting Western Vimentin 030204 cardiovascular system & hematology Iliac Artery Calcification 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Gene expression medicine Humans Vascular remodeling Gene Regulatory Networks RNA Messenger Mammary Arteries Renal Insufficiency Chronic Uremia Aged Oligonucleotide Array Sequence Analysis Kidney biology business.industry Gene Expression Profiling Middle Aged medicine.disease Atherosclerosis Immunohistochemistry 030104 developmental biology medicine.anatomical_structure Cross-Sectional Studies Case-Control Studies Creatinine biology.protein Female business Transcriptome Biomarkers Kidney disease |
| Zdroj: | Stubbe, J, Skov, V, Thiesson, H C, Larsen, K E, Hansen, M L, Jensen, B L, Jespersen, B & Rasmussen, L M 2018, ' Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease ', American Journal of Physiology: Renal Physiology, vol. 314, no. 6, pp. F1117-F1128 . https://doi.org/10.1152/ajprenal.00418.2017 Stubbe, J, Skov, V, Thiesson, H, Larsen, K E, Hansen, M L, Jensen, B L, Jespersen, B & Rasmussen, L M 2017, ' Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease ', 21st annual meeting of the European Council for Cardiovascular Research (ECCR 2017), Italien, 20/10/2017-22/10/2017 . |
| ISSN: | 1522-1466 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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