title: Endothelial heparanase regulates heart metabolism by stimulating lipoprotein lipase secretion from cardiomyocytes.
abstract: OBJECTIVE
  After diabetes mellitus, transfer of lipoprotein lipase (LPL) from cardiomyocytes to the coronary lumen increases, and this requires liberation of LPL from the myocyte surface heparan sulfate proteoglycans with subsequent replenishment of this reservoir. At the lumen, LPL breaks down triglyceride to meet the increased demand of the heart for fatty acid. Here, we examined the contribution of coronary endothelial cells (ECs) toward regulation of cardiomyocyte LPL secretion.
  
  
  RESULTS
  Bovine coronary artery ECs were exposed to high glucose, and the conditioned medium was used to treat cardiomyocytes. EC-conditioned medium liberated LPL from the myocyte surface, in addition to facilitating its replenishment. This effect was attributed to the increased heparanase content in EC-conditioned medium. Of the 2 forms of heparanase secreted from EC in response to high glucose, active heparanase released LPL from the myocyte surface, whereas latent heparanase stimulated reloading of LPL from an intracellular pool via heparan sulfate proteoglycan-mediated RhoA activation.
  
  
  CONCLUSIONS
  Endothelial heparanase is a participant in facilitating LPL increase at the coronary lumen. These observations provide an insight into the cross-talk between ECs and cardiomyocytes to regulate cardiac metabolism after diabetes mellitus.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Dahai
authors.initials: D
authors.lastname: Zhang
authors.forename: Amy Pei-Ling
authors.initials: AP
authors.lastname: Chiu
authors.forename: Andrea
authors.initials: A
authors.lastname: Wan
authors.forename: Katharina
authors.initials: K
authors.lastname: Neumaier
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology*; D005966:Glucuronidase / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020742:rhoA GTP-Binding Protein / Q000502:physiology; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D008071:Lipoprotein Lipase; D051571:Protein Kinase C-alpha; D020742:rhoA GTP-Binding Protein; D000099175:Heparanase