Understanding how blood flow causes vessel damage in atherosclerosis

Role of the mechanoreceptor Pkd1 in endothelial dysfunction and atherosclerosis

Atherosclerosis – the build-up of fatty deposits in the arteries – tends to develop in areas where the blood vessels are exposed to stress caused by changes in blood flow. This causes cells that line the blood vessel to die off, which further contributes to the damage in the vessel wall. Exactly how blood vessel cells translate the impact of blood flow – a mechanical event – into a biological signal that tells cells to die off, is not fully understood. But Dr Serbanovic Canic has used zebrafish to study molecules called ‘mechanoreceptors’ which are thought to translate this signal. She has identified one mechanoreceptor called polycystin-1 (Pkd1) and has shown that, when Pkd1 is deleted in mice, there are higher amounts of blood vessel cell death. This suggests that Pkd1 may normally protect blood vessel cells from damage. In this project, Dr Serbanovic Canic is exploring the role of Pkd1 further. She will engineer mice so that Pkd1 is deleted only from their blood vessel cells. This will reveal its role in the development of atherosclerosis. She is also using a state-of-the-art technique called RNA sequencing to determine the genes that are controlled by Pkd-1. The hope is that it may be possible to identify molecules downstream from Pkd1 that can be targeted to treat atherosclerosis.