Gene expression profiling of aortic smooth muscle cells treated with a novel H2S-based compound

Abstract

Despite improved healthcare and medical knowledge, cardiac failures after operation are still an important problem. Therefore, interest in alternative treatments like the use of gasotransmitters is high. Gasotransmitters are a novel class of pharmaceutically relevant components which can quickly induce complex biological responses in cells. H2S, the newest member, exhibits anti-inflammatory and anti-apoptotic proper-ties but is also toxic at higher concentrations. Thus, the need for a reliable H2S donor is given. One candidate could be the compound SWS95.HCl, a H2S/COS donor which exhibits additional vasodilatory effects on aortic smooth muscle cells (HCASMC). However, the underlying molecular mechanisms remain unclear so far. Hence, a whole genome approach was chosen to further elucidate the mode of action of SWS95.HCl on HCASMC cells. To study early and late responses alike, time-course experiments were performed and changes in the gene expression patterns were detected by microarray technology. To ensure the relevance of the subsequent analysis, evaluation of data prefiltering as well as comparison of two different statistical analysis methods was performed. Data analysis revealed the upregulation of a variety of genes in biological categories related to anti-apoptosis, smooth muscle contraction and angiogenesis. Furthermore, we showed an enhanced gene expression profile in pathways associated with ischemic preconditioning. SWS95.HCl is therefore a promising candidate for further drug development to treat cardio-vascular diseases.