Biomedical subjects

Mathias Gebauer

Publications and source records attributed to Mathias Gebauer.

5 recordsLinked to original sources

PubMed2005

Functional profiling of human atrial and ventricular gene expression.

The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions. Moreover, as major functional classes of atrial- and ventricular-specific transcripts were common to human and murine myocardium, an evolutionarily conserved chamber-specific expression pattern in mammalian myocardium is suggested.

Animals↗

PubMed2005

Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature.

Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium.

Atrial Fibrillation↗

PubMed2005

Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage.

Osteoarthritis is the most common degenerative disorder of the modern world. However, many basic cellular features and molecular processes of the disease are poorly understood. In the present study we used oligonucleotide-based microarray analysis of genes of known or assumed relevance to the cellular phenotype to screen for relevant differences in gene expression between normal and osteoarthritic chondrocytes. Custom made oligonucleotide DNA arrays were used to screen for differentially expressed genes in normal (n = 9) and osteoarthritic (n = 10) cartilage samples. Real-time polymerase chain reaction (PCR) with gene-specific primers was used for quantification. Primary human adult articular chondrocytes and chondrosarcoma cell line HCS-2/8 were used to study changes in gene expression levels after stimulation with interleukin-1beta and bone morphogenetic protein, as well as the dependence on cell differentiation. In situ hybridization with a gene-specific probe was applied to detect mRNA expression levels in fetal growth plate cartilage. Overall, more than 200 significantly regulated genes were detected between normal and osteoarthritic cartilage (P < 0.01). One of the significantly repressed genes, Tob1, encodes a protein belonging to a family involved in silencing cells in terms of proliferation and functional activity. The repression of Tob1 was confirmed by quantitative PCR and correlated to markers of chondrocyte activity and proliferation in vivo. Tob1 expression was also detected at a decreased level in isolated chondrocytes and in the chondrosarcoma cell line HCS-2/8. Again, in these cells it was negatively correlated with proliferative activity and positively with cellular differentiation. Altogether, the downregulation of the expression of Tob1 in osteoarthritic chondrocytes might be an important aspect of the cellular processes taking place during osteoarthritic cartilage degeneration. Activation, the reinitiation of proliferative activity and the loss of a stable phenotype are three major changes in osteoarthritic chondrocytes that are highly significantly correlated with the repression of Tob1 expression.

Adult↗

PubMed2004

Microarray applications: emerging technologies and perspectives.

Highlights of the EuroBiochips conference, which was held in Hamburg, Germany, on 22-24 June 2004. Topics addressed at the meeting included the uses of padlock probes and nanomechanical cantilevers and microarray applications for patient profiling.

Gene Expression Profiling↗

PubMed2004

Global gene expression in human myocardium-oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure.

To obtain region- and disease-specific transcription profiles of human myocardial tissue, we explored mRNA expression from all four chambers of eight explanted failing [idiopathic dilated cardiomyopathy (DCM), n=5; ischemic cardiomyopathy (ICM), n=3], and five non-failing hearts using high-density oligonucleotide arrays (Affymetrix U95Av2). We performed pair-wise comparisons of gene expression in the categories (1) atria versus ventricles, (2) disease-regulated genes in atria and (3) disease-regulated genes in ventricles. In the 51 heart samples examined, 549 genes showed divergent distribution between atria and ventricles (272 genes with higher expression in atria, 277 genes with higher expression in ventricles). Two hundred and eighty-eight genes were differentially expressed in failing myocardium compared to non-failing hearts (19 genes regulated in atria and ventricles, 172 regulated in atria only, 97 genes regulated in ventricles only). For disease-regulated genes, down-regulation was 4.5-times more common than up-regulation. Functional classification according to Gene Ontology identified specific biological patterns for differentially expressed genes. Eleven genes were validated by RT-PCR showing a good correlation with the microarray data. Our goal was to determine a gene expression fingerprint of the heart, accounting for region- and disease-specific aspects. Recognizing common gene expression patterns in heart failure will significantly contribute to the understanding of heart failure and may eventually lead to the development of pathway-specific therapies.

Adult↗