Metabolic syndrome is a cluster of several risk factors for type 2 diabetes and cardiovascular disease, including obesity, hypertension, insulin resistance, and dyslipidemia. These pathological conditions are determined multifactorially by many genes and their interactions with environmental effects. Genome wide association studies (GWAS) in humans which are based on the “common variants – common diseases“ hypothesis identified only a minor proportion of the total heritability of complex traits so far.

Statistically significant variants (SNPs – single nucleotide polymorphisms) are typically associated with a miniscule phenotypic variability without meaningful clinical effects. Studies in animal models of human complex diseases can provide a useful alternative. Experiments with rat models can control for both genetic background and environmental effects as well as enable genetic manipulation of experimental animals. The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and associated metabolic disturbances typical for metabolic syndrome. Although it cannot be expected that the individual predisposing genes themselves might be conserved between rats and humans, it is likely that the networks and pathways of genes leading to disease susceptibility will be conserved across species. Therefore, identification of the networks and pathways of genes underlying the cellular pathology of disease phenotypes in the rat could provide insight into the pathogenesis and treatment of the corresponding human diseases.

Our research is focused on these projects:

• Identification of genes that regulate hemodynamic and metabolic traits in the SHR.
• Identification of new genes coding for mitochondrial proteins and their role in the pathogenesis of metabolic syndrome.
• Derivation of new animal models using highly effective methods for transgenesis and gene targeting.
• Study of the role of inflammatory processes and oxidative stress in the pathogenesis of metabolic syndrome and possibility of pharmacologic interventions.

Current grant support.