Gene expression profiling analysis shows differential expression of extracellular matrix genes in left ventricular hypertrophy of renal failure

Christian Maercker
Resource Center for Genome Research
German Cancer Research Center H0600
Im Neuenheimer Feld 280
D-69120 Heidelberg
Germany
telephone: +49 6221 424741
fax: +49 6221 423454
email: c.maercker@dkfz.de
prestype: Platform
presenter: Christian Maercker

Christian Maercker¹, Diana Lutz¹, Eberhard Ritz², Gerhard Mall³, Kerstin Amann⁴
Resource Center for Genome Research (RZPD)¹, Heidelberg, Dept. of Internal Medicine², University of Heidelberg, Heidelberg, Dept. of Pathology³, Darmstadt, Department of Pathology⁴, University of Erlangen, Erlangen,

Aims: Death from cardiac causes is the leading fatality in patients with chronic renal failure. In particular, left ventricular hypertrophy (LVH) is a frequent alteration which develops very early on in pa-tients and rats with renal failure. The pathomechanisms involved, however, are currently not fully understood. Thus, additional information from gene expression profiling could be extremely helpful.

Methods: Male Sprague-Dawley rats, which were subjected to sub-total nephrectomy (SNX), served as a model system for a gene expression profiling analysis. Poly(A)+ RNA from the hearts of SNX animals and from sham-operated rats (SHAM) as a control, isolated 2 weeks and 12 weeks after operation, was labeled and hybridized with Rat UniGene filters containing about 27.000 gene and EST sequences (Bento Soares, Univ. of Iowa). Phosphoimaging and software analysis revealed substantial changes in gene expression in SNX animals compared to SHAM.

Results: Interestingly, some genes were upregulated in SNX rats, which may be involved in activation and expansion of the non-vascular interstitial tissue in uraemic animals. These include genes like timp3, tgf-b1, osteonectin, paxillin, laminin a1, integrin b. Altogether 80 genes were found at least 3fold under or overexpressed. By hybridization of the RNA to human and mouse arrays (Human UniGene RZPD-1, 33.000 clones; Mouse UniGene RZPD-1, 25.000 clones) we could confirm the results with genes which are conserved between human, rat and mouse.

Conclusions: The findings showed (i) that extracellular matrix genes are differentially expressed in LVH of renal failure and that (ii) the complex hybridisation technique produced reliable results. This is an important prerequisite for ongoing experiments with candidate genes involved in cardiac structural changes in chronic renal failure.