Abstract 13631: Endothelial Lipase in the Heart Modulates Pressure Overload-Induced Heart Failure through Fatty Acid Utilization
Aims: Under normal circumstances,nearly 70% of the cardiac energy substrates are derived from the oxidation of fatty acid (FA). Triglyceride lipase members are essential for the generation of lipid-derived FA. Lipoprotein lipase (LPL), which hydrolyzes triglyceride-rich lipoproteins, has been considered as the only enzyme capable of this function in the heart. Endothelial lipase (EL) exhibits primarily phospholipase activity against high-density lipoproteins, but to a lesser extent, triglyceride lipase activity. Although EL is expressed in the heart, the function of EL in this tissue remains unclear. In this study, we assessed the role of EL in the heart under conditions of increased energy needs.
Methods and Results: Pressure overload-induced cardiac hypertrophy was generated in EL-/- and C57Bl/6 wild-type (WT) mice by ascending aortic banding. EL expression in cardiac tissues was significantly elevated in the early stage of cardiac hypertrophy in WT mice, while LPL expression was significantly reduced. Next, we examined the effect of EL deletion on cardiac adoptive responses to pressure overload. In response to the aortic banding, EL-/- mice showed severer systolic dysfunction with left ventricular dilatation compared with WT mice, while the degree of hypertrophy was similar between WT and EL-/- mice. The expression of mitochondrial FA oxidation-related genes, such as carnitine palmitoyltransferase-1 and medium-chain acyl CoA dehydrogenase, was significantly lower in the heart of EL-/- mice than that in WT mice. Also, myocardial ATP levels in EL-/- mice were lower than in WT mice after aortic banding. Complementary cell culture experiments using rat neonatal cardiac myocytes revealed that EL was upregulated by inflammatory cytokines and lipopolysaccharide in sharp contrast that LPL was downregulated. Incubation of EL-overexpressing cardiac myocytes with HDL resulted in an increase in lipid uptake, upregulation of FA oxidation-related enzymes, and intracellular ATP accumulation.
Conclusion: We have provided a novel finding that EL may be an alternative candidate to provide FA to the heart and regulate cardiac function. This effect seemed relevant particularly under the inflammatory condition where the action of LPL is downregulated.
- © 2012 by American Heart Association, Inc.