Heart disease remains the most common cause of death and disability in our society. However, the face of this disease has evolved considerably in the decades since cardiovascular scientists began to understand the cellular and molecular mechanisms of its pathophysiology. Today, nearly 90% of patients hospitalized for a heart attack not only survive but also return to their normal activities and work within weeks, if not sooner — a vast improvement in outcome as compared with decades earlier. However, the evolution in the treatment of acute cardiovascular disease has also been paralleled by an increase in the number of patients with chronic debilitation due to heart failure. Despite advances in our understanding of the neurohormonal basis of heart failure, current therapies for heart failure are limited, and the need for additional therapies remains great. Protein homeostasis plays a role in the development of numerous disorders. Misfolded proteins are central in the pathophysiology of neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease. In the past several years, misfolded proteins have been found to play a role in the pathophysiology of common human cardiac diseases such as pathologic cardiac hypertrophy and dilated and ischemic cardiomyopathies, leading to the suggestion that protein misfolding is a key contributor to the progression of heart failure. In this review, we explore the contribution of protein misfolding to the pathophysiology of cardiac disease, describing why these proteins become misfolded and how the innate systems that usually dispose of them break down. We then discuss how the knowledge obtained from studying protein misfolding in other diseases, such as Alzheimer’s disease, may aid us in understanding the pathophysiological mechanisms of cardiac diseases and developing new treatments that focus on preventing or reversing protein misfolding in the heart.
Monte S. Willis & Cam Patterson
New England Journal of Medicine, Jan 31, 2013