Coronary heart disease, also known as ischemic heart disease, is the most common cause of death worldwide, primarily due to heart failure following a heart attack, or myocardial infarction (MI). Necroptosis, a regulated form of cell death, is known to play an important role in heart damage during MI.

In a new study, Richard N. Kitsis, M.D., and colleagues report that the pathway by which necroptosis was assumed to operate during MI is incorrect. Rather than the protein RIPK1 initiating the cascade of signaling events, they discovered that the protein ZBP1 is responsible. ZBP1 is a cellular sensor of DNA and double-stranded RNA in the unconventional “left-handed” conformation, possibly implicating these nucleic acids in ischemic signaling. This work is an important step toward understanding how cell death occurs during MI and, therefore, might be targeted with drugs to reduce mortality from coronary heart disease. The study, titled “Reformulation of the Necroptosis Pathway in Reperfused Myocardial Infarction,” published online on August 18 in Circulation.

Dr. Kitsis is professor of medicine and of cell biology, the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease, and director of the Wilf Family Cardiovascular Research Institute at Einstein. Dr. Kitsis is also a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center and of the Einstein-Mount Sinai Diabetes Research Center.