Key result
Exposure of coronary endothelial cells to high glucose stimulated heparanase secretion, which liberated lipoprotein lipase from the cardiomyocyte surface and facilitated its intracellular replenishment.
Endothelial heparanase plays a key role in regulating cardiac metabolism after diabetes by facilitating lipoprotein lipase increase at the coronary lumen.
Heparanase may mediate hyperglycemia-driven cardiac lipid shifts in diabetes; leaves open its therapeutic targeting in human cardiomyopathy.
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. APPROACH AND 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.
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Wang et al. (2013) studied Diabetes mellitus. High glucose was evaluated on Lipoprotein lipase (LPL) liberation and replenishment in cardiomyocytes. Exposure of coronary endothelial cells to high glucose stimulated heparanase secretion, which liberated lipoprotein lipase from the cardiomyocyte surface and facilitated its intracellular replenishment.
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