Project 452726

Recent studies have shown a linkage between severe influenza (the flu) infection and heart attacks. Studies on Canadian patients have determined that individuals with underlying health risks (atherosclerosis) experience more than a 6-fold increased risk of a heart attack in the 7 days following hospital admission for severe flu infections. This creates an important problem; how does an infection in a patient's lungs trigger a life-threatening event in the heart. We propose that molecules produced to regulate inflammation in the lungs circulate in the blood where they activate cells in the blood vessels of the heart trigger damage, blood clotting, blockages and a heart attack. We will study inflammation in the blood vessels and heart of at-risk mice infected with flu, immune proteins in the blood of patients infected with flu, and studies to understand blood vessel activation and damage in biopsies taken from at-risk patients with underlying conditions (atherosclerosis). We will use state-of-the-art microscopes that can see individual immune cells in the blood vessels and heart of living mice (intravital microscopy), allowing us to understand how immune cells are activated and how these cells damage the blood vessels. Using a second microscope, we will be able to study the changes to the blood vessel wall that allows us to see structures that are even smaller than cells (super-resolution microscopy). This unique combination of imaging approaches will provide insight and understanding of the biological processes linking flu infection and heart attacks at a level of detail never-before possible with more conventional lab techniques. By understanding which molecules activate the heart blood vessels in at risk people, and understanding how this activation occurs, we aim to design therapies to prevent these infection-induced heart attacks. Development of new therapies will reduce the risk of heart attack in susceptible patients, improve outcomes and save lives.