Gene expression profiling in three primary human cell lines treated with atorvastatin or an inhibitor of Rho kinase. Homo sapiens

Inhibitors of Rho kinase (ROCK) are a new class of drugs with potential benefit in oncology, neurology, and fibrotic and cardiovascular diseases. ROCK inhibitors modulate many cellular functions, some of which are similar to the pleiotropic (non-lipid lowering) effects of statins, suggesting additive or synergistic properties. Studies to date have used compounds which inhibit both isoforms of ROCK, ROCK1 and ROCK2. In this study, the effect of the newly developed ROCK2 inhibitor SLx-2119 on genome-wide gene expression was compared with atorvastatin in primary human cells. Keywords: Cell type comparison, agent comparison Overall design: Primary cultures of human microvascular endothelial cells HMVEC), human pulmonary artery smooth muscle cells (PASMC), and normal human dermal fibroblasts (NHDF) were treated with SLx-2119 or atorvastatin for 24 hours, after which total RNA was isolated and gene expression profiles were obtained with Illumina BeadChips. Reversing the effects of statins by the addition of mevalonate provides an opportunity to subtract non-specific effects of statins in vitro. This approach was also used in the current study, as follows: cells were treated with a combination of atorvastatin and mevalonate and genes were considered up- or down-regulated when the addition of mevalonate significantly reversed the change in expression observed in atorvastin-treated cells.