Grant: Project Grant

The development of cardiovascular diseases such as hypertension, atherosclerosis and heart failure has often been associated with impaired function of cell surface proteins named receptors. These are the targets of more than 50% of all drugs sold today. Blocking the activation of the receptor often results in important sides effects. Therefore, the identification of new intracellular pharmacological targets will allow us to design more effective and specific drugs to treat cardiovascular diseases. For the last 12 years, we have engaged in the study of an intracellular protein that is activated by hormone stimulation. We have shown that this protein named ARF6 is a central regulator of several cellular responses misregulated in cardiovascular diseases. Our findings indicate that this protein could be an interesting new drug target. We propose here to further study its function in cells of the vasculature in order to further demonstrate its key role in responses altered in pathology. In this project, our main goal is to study the function of ARF6 in vascular smooth muscle cells. These constitute the main body of cells in arteries and are responsible for the contractile response. Our main hypothesis is that the intracellular protein ARF6 is a key regulator of the most important vasoactive substance. It is therefore fundamental to delineate and understand the role of ARF6 as a future drug targets in order to minimize adverse effects of newly designed drugs. The first objective of our research project is to elucidate the molecular mechanisms by which ARF6 regulates the most important cellular responses that are altered in disease. These are complete change of phenotypic features that leads to increase growth, motility and free radicals. Next, we propose to engineer new animal models to study the ARF6 gene in vivo. We will be able to study these animals and understand the role our protein of interest plays in normal physiology but also in disease.