Grant: Operating Grant

The heart uses fat as a source of energy to help maintain its ability to pump blood efficiently. The contractile cells of the heart have a protein called CD36 that plays a major role in taking up fat into the cell. Notwithstanding the importance of the use of fat for energy, pre-clinical evidence has suggested that partial inhibition of the use of fat for energy in the heart can prevent injury to the heart. In addition, people with heart disease can also be prescribed drugs that partially inhibit the use of fat for energy and these treatments show benefit to the function of the heart. That said, there is controversy as to whether these drugs actually partially inhibit the use of fat for energy or whether they have benefits via altering other unrelated pathways. As a result, it is unclear as to whether partially inhibiting the use of fat for energy is truly beneficial to the injured or diseased heart. In addition to the uncertainty about the benefits of the use of fat for energy, there is also a growing body of evidence suggesting that this approach may actually contribute to poor function of the heart (in all instances but especially in diabetic patients). Based on this, we will test whether inhibition of CD36 function (which will decrease fat uptake into the heart as well as limit the use of fat for energy) is beneficial or detrimental to the heart in a variety of diseased states. These studies will ultimately lead to a better understanding of the importance of CD36 in the heart as well as allow us to ascertain whether drugs designed to inhibit CD36 in the heart (or related pathways that partially inhibit the use of fat for energy) may contribute to improving the performance of the heart in patients with heart disease and/or diabetes.