Regulation and Remodeling of Membrane Microdomains of Cardiomyocytes During Heart Failure Progression

Millions of people worldwide live with heart failure, meaning their hearts can't pump blood through the body as well as they should. That can lead to fatigue and shortness of breath, as the body struggles to get the oxygen it needs. Heart failure is a chronic, progressive condition, and as the heart weakens, everyday activities can become difficult. Some patients eventually require a heart transplant or a surgically implanted device like a defibrillator or a left ventricular assist device to survive. At U of U Health, scientists are learning how the molecular organization of heart cells changes as heart failure progresses, and using that knowledge to pioneer potential gene therapy for heart disease. Associate Professor of Pharmacology and Toxicology TingTing Hong, PhD, and Robin Shaw, MD, PhD, director of the Nora Eccles Harrison Cardiovascular Research and Training Institute have zeroed in on a protein that helps organize molecules and channels on the outer surface of the heart's muscle cells that are critical for coordinating the heart's rhythmic contractions. Levels of that protein, cBIN1, tend to decline with heart failure, worsening the condition. Hong, Shaw and colleagues have found that gene therapy that restores cBIN1 can improve heart function in laboratory animals with heart failure. They've had success using cBIN1 gene therapy to restore function in animals whose hearts have been damaged by a lack of blood flow, similar to the myocardial ischemia patients can experience when an artery is blocked, as well as in non-ischemic cardiac myopathy. Their findings in animal models have paved the way to developing an innovative gene therapy for patients.