Grant: Project Grant

Blood vessels control blood flow by altering their diameter. In the brain, this process ensures that every region receives enough blood for its metabolic needs. Heart disease changes how blood vessels control their diameter and hence, blood flow. We show that brain perfusion is reduced in heart failure, which over time, causes serious effects. It is therefore important to better understand how blood vessels control their diameter in both health and disease. Since patients with heart failure have a higher risk for stroke and neurological problems, this knowledge will help improve the medical treatment of heart disease. In experimental models, heart failure causes brain blood vessels to become smaller. As a result, blood flow is reduced and brain injury occurs. We have identified a protein, named the "cystic fibrosis transmembrane conductance regulator (CFTR)" that under normal conditions keeps blood vessels in an open state. In heart failure, the amount of this protein in blood vessels is reduced. There are medications that restore the normal function of CFTR. Currently, these medications are not used in heart failure patients (they are exclusively used to treat cystic fibrosis). Our objective is to show that these medications restore blood vessels to their normal size in heart failure and understand how they do it. If these medications work as predicted, we should see better brain blood flow in heart failure patients. Some of our experiments will use genetically modified mice, which are expected to behave differently by not responding to the drugs. If successful, we will introduce a new therapy for a serious heart failure complication. Our research advances fundamental concepts in how blood vessels in the brain work. By doing so, this research will improve the health of Canadians with heart failure.