Grant: Operating Grant

Heart failure is a devastating cardiovascular disease. Patients with heart failure have an increased risk of stroke and often develop neurological symptoms. Despite its clinical importance, the mechanisms that link heart failure to neurological problems are not understood. We believe that a reduction in blood flow to the brain is responsible for the neurological symptoms that ultimately develop. Our group demonstrates that blood flow within the brain is reduced in mice with heart failure and has identified key signalling mechanisms that cause cerebral arteries to constrict. Tumour necrosis factor (TNF) and sphingosine-1-phosphate are key mediators in this signalling pathway; both are well-studied entities. The core objectives of this proposal are to (i) to integrate these characterized molecular mechanisms into the more complex whole animal setting, in order to directly relate changes in vascular function to altered blood flow and (ii) assess the effectiveness of medications that could potentially be used as clinical therapies in the future. A better understanding of these mechanisms will lead to the establishment of preventative measures that will improve the health of those suffering from heart failure.