Project Description Narrative:
Heart disease is the leading cause of death and disability in Wisconsin, taking over 16,000 lives each year (Wisconsin Department of Health Services, 2017 statistics). The impacts of cardiovascular diseases on families are huge, both emotionally and economically. It is estimated that heart diseases cost over $7.5 billion per year for families and the health care system of Wisconsin. Myocardial infarction, also known as a “heart attack,” is the most common form of fatal heart disease in Wisconsin.
Although most patients survive a heart attack, the adult human heart fails to appropriately heal after a heart attack, and many individuals who have experienced a heart attack will develop progressive heart failure. Patients who progress to end stage heart failure are limited to costly and sometimes problematic treatments such as heart transplant or implantation of left ventricular assist device, which is a device that partially or completely replaces the function of the failing heart. In fact, among people 45 years old and above in Wisconsin, 36% of men and 47% of women will die within five years after their first heart attack.
Thus, there is great interest in identifying alternative therapies for treating heart failure in humans.
Heart failure as a result of a heart attack is largely attributed to the massive loss of functional heart muscle cells, the cardiomyocytes, and excessive and uncontrolled scarring response from fibroblasts, a type of supporting cell in the heart. Researchers involved in this study propose a strategy to convert local fibroblasts in the heart into functional cardiomyocytes, so called “direct cardiac reprogramming,” to improve cardiac functional recovery and meanwhile control fibrosis.
With the key molecular barriers identified, improved human direct cardiac reprogramming has the potential to provide new cardiomyocytes and at the same time slow down fibrosis, leading to a promising strategy for treating heart diseases.