Principal Investigator: Dr Piruthivi Sukumar
Institution: University of LeedsTags: 42651, cardiovascular disease, exercise, mechanosensor, piezo1
Cardiovascular Diseases (CVD) – which compromise oxygen and nutrient supply by reduction in blood supply to various organs, such as heart attack and stroke are one of the leading causes of morbidity and mortality in the UK and worldwide. When blood is pumped into blood vessels by the heart and flows through, it exerts mechanical pressure on to the inner lining of vascular wall. Until recently, the identity of the proteins that sense such mechanical force in animal cells was unknown. Now it has been discovered that Piezo1, a protein which forms non-selective cation permeable pores on the cellular membranes are the mechanical sensors in different mammalian cells including human vascular cells. Also, various mutations have been described in Piezo1 and many of them cause significant diseases in humans including anaemia, generalized lymphatic dysplasia and colorectal polyps. Importantly, we have showed that Piezo1 is essential for new blood vessel formation in murine embryos, for blood pressure in exercising adult mice, and for improving exercise capacity by diverting blood from gut to skeletal muscle in adults. Here we propose to analyse mutations (single nuclear polymorphisms) in coding and non-coding regions of PIEZO1 gene in general population to identify whether there is any link between Piezo1 mutations and CVD and exercise tolerance.