Grant: Proof of Principle Program - Phase I

The heart is a large active muscle whose cells generate energy to pump blood around the body from two kinds of fuels: fats (fatty acids) and sugar (glucose). It has been shown that there are advantages for a damaged or diseased heart to burn more glucose and less fatty acid. As such, any treatment that shifts fuel use from fatty acids to glucose is potentially beneficial to the heart, especially when diseased. We have engineered a family of large polymeric molecules called derivatized hyperbranched polyglycerols (dHPGs) that can bind fatty acids in the blood and, therefore, have the capability of reducing availability of fatty acids to heart muscle cells. In previous experiments in our laboratory, we found that dHPGs reduce fatty acid use and increase glucose in heart muscle. Additionally, we have preliminary evidence that suggests this same treatment helps hearts recover better after a heart attack, when blood supply to the heart is temporarily arrested. The dHPGs have been shown to be very safe and do not cause unwanted responses. The experiments in the present application will confirm if dHPGs are truly beneficial after a heart attack and will also delineate the specific manner in which they reduce fatty acid use by heart muscle.