title: Endothelial lipase modulates pressure overload-induced heart failure through alternative pathway for fatty acid uptake.
abstract: Lipoprotein lipase has been considered as the only enzyme capable of generating lipid-derived fatty acids for cardiac energy. Endothelial lipase is another member of the triglyceride lipase family and hydrolyzes high-density lipoproteins. Although endothelial lipase is expressed in the heart, its function remains unclear. We assessed the role of endothelial lipase in the genesis of heart failure. Pressure overload-induced cardiac hypertrophy was generated in endothelial lipase(-/-) and wild-type mice by ascending aortic banding. Endothelial lipase expression in cardiac tissues was markedly elevated in the early phase of cardiac hypertrophy in wild-type mice, whereas lipoprotein lipase expression was significantly reduced. Endothelial lipase(-/-) mice showed more severe systolic dysfunction with left-ventricular dilatation compared with wild-type mice in response to pressure overload. The expression of mitochondrial fatty acid oxidation-related genes, such as carnitine palmitoyltransferase-1 and medium-chain acyl coenzyme A dehydrogenase, was significantly lower in the heart of endothelial lipase(-/-) mice than in wild-type mice. Also, endothelial lipase(-/-) mice had lower myocardial adenosine triphosphate levels than wild-type mice after aortic banding. In cultured cardiomyocytes, endothelial lipase was upregulated by inflammatory stimuli, whereas lipoprotein lipase was downregulated. Endothelial lipase-overexpression in cardiomyocytes resulted in an upregulation of fatty acid oxidation-related enzymes and intracellular adenosine triphosphate accumulation in the presence of high-density lipoprotein. Endothelial lipase may act as an alternative candidate to provide fatty acids to the heart and regulate cardiac function. This effect seemed relevant particularly in the diseased heart, where lipoprotein lipase action is downregulated.
authors: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Hideto
authors: H
authors: Nakajima
authors: Tatsuro
authors: T
authors: Ishida
authors: Seimi
authors: S
authors: Satomi-Kobayashi
authors: Kenta
authors: K
authors: Mori
authors: Tetsuya
authors: T
authors: Hara
authors: Naoto
authors: N
authors: Sasaki
authors: Tomoyuki
authors: T
authors: Yasuda
authors: Ryuji
authors: R
authors: Toh
authors: Hidekazu
authors: H
authors: Tanaka
authors: Hiroya
authors: H
authors: Kawai
authors: Ken-ichi
authors: K
authors: Hirata
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006332:Cardiomegaly / Q000503:physiopathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D006333:Heart Failure / Q000209:etiology* / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology*; D008049:Lipase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D008049:Lipase; C498741:Lipg protein, mouse