Grant: Operating Grant

The development of cardiovascular diseases such as atherosclerosis 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. Receptors are activated mainly by stimuli such as circulating hormones, which initiate a broad variety of intracellular signaling cascades leading to a subset of cellular responses such as cell migration and growth. Blocking the activation of the receptor often results in important sides effects. The identification of new intracellular pharmacological targets will allow us to design more effective and specific drugs. For the last 8 years, we have engaged, through funding by CIHR, 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. Here, we propose to study its role in cellular as well as tissue responses of the cardiovascular system. First, we will examine how exactly these proteins are activated following angiotensin II stimulation, a potent vasoactive hormone. Next, we will examine the role of ARF6 in regulating cell migration, invasion, proliferation and contraction in cells of the vascular wall as well as tissue responses. Altogether, our findings will further our understanding of the role of ARF proteins but, most importantly, will help us develop more specific new drugs and directly contribute to improve health of Canadians.