Cardiovascular drug target discovery: In vitro and in vivo validation studies

Abstract

Despite the increase in knowledge about cardiovascular diseases and the increase in available drugs since the beginning of the 20th century, one out of three people still dies from cardiovascular diseases. In more than 50% of all cases, atherosclerosis is the underlying pathology and therefore, it is of great importance to develop better cardiovascular drugs. The research described in this dissertation focusses on the discovery and validation of novel targets for cardiovascular drugs. Of the three possible targets that were investigated, oncostatin M was most thoroughly investigated. The researchers showed that this protein is expressed in the blood vessel wall at atherosclerotic lesion sites and that oncostatin M induces endothelial activation. Endothelial cells line the inner blood vessel wall and activation of these cells is often the first step in atherosclerosis development. These observations indicate that oncostatin M enhances atherosclerosis development. However, this hypothesis could not be confirmed in a study in mice. Against all expectations, mice treated with oncostatin M showed smaller atherosclerotic lesions than their littermates that were not treated with oncostatin M. Further research is required to define the exact role of oncostatin M in atherosclerosis before it can truly be considered as a novel target against cardiovascular diseases.