title: Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy.
abstract: Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. To study whether nontransferable lipoprotein lipase has physiological actions, we placed an alpha-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered lipoprotein lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.
authors.affiliation: Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yagyu
authors.forename: Guangping
authors.initials: G
authors.lastname: Chen
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hirata
authors.forename: Ayanna
authors.initials: A
authors.lastname: Augustus
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kako
authors.forename: Toru
authors.initials: T
authors.lastname: Seo
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.forename: E Peer
authors.initials: EP
authors.lastname: Lutz
authors.forename: Martin
authors.initials: M
authors.lastname: Merkel
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology*; D003402:Creatine Kinase / Q000378:metabolism; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D004452:Echocardiography; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009206:Myocardium / Q000166:cytology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014162:Transfection; D024723:Ventricular Myosins / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D003402:Creatine Kinase; D008071:Lipoprotein Lipase; D024723:Ventricular Myosins