Grant: Operating Grant

The high energy demands of the heart are met by the metabolism of both sugars and fatty acids. Normally, there is a balance between the use of these sugars and fatty acids. However, if blood flow to the heart muscle is interrupted,such as occurs during a heart attack, oxygen supply to the heart is interrupted and energy supply to the muscle is compromised. If blood flow is then re-introduced to the muscle, called "reperfusion", alterations in the control of energy metabolism occur, such that fatty acids dominate as a source of fuel. This unfortunately occurs at the expense of sugar use. This excessive use of fatty acids compromises the ability of the heart to recover from the heart attack. Our research has shown that a major contributor to this excessive use of fatty acids is due to excessive uptake of fatty acids by the mitochondria of the heart, which are the "furnaces" that produce the energy the heart needs to function. This excessive uptake of fatty acids by the mitochondria, has the consequence of making the heart less efficient at producing energy. This inefficient production of energy can be very harmful for the heart following a heart attack, and can cause injury and death of the heart muscle. The studies proposed in this grant application will determine what is responsible for this excessive mitochondrial uptake of fatty acids, including the role of a newly identified process in which proteins involved in energy metabolism become acetylated following ischemia. We will also determine if preventing the switch from sugar to fatty acid metabolism can be used as a therapeutic strategy to protect the heart following a heart attack or following cardiac surgery. Understanding how energy metabolism is regulated in heart should lead to the development of therapies that optimize energy use by the heart and protect the heart following a heart attack or following cardiac surgery.