Advertisement

Research Article Free access | 10.1172/JCI118479

Hepatic lipase gene therapy in hepatic lipase-deficient mice. Adenovirus-mediated replacement of a lipolytic enzyme to the vascular endothelium.

D Applebaum-Bowden, J Kobayashi, V S Kashyap, D R Brown, A Berard, S Meyn, C Parrott, N Maeda, R Shamburek, H B Brewer Jr, and S Santamarina-Fojo

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Applebaum-Bowden, D. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Kobayashi, J. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Kashyap, V. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Brown, D. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Berard, A. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Meyn, S. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Parrott, C. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Maeda, N. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Shamburek, R. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Brewer, H. in: PubMed | Google Scholar

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.

Find articles by Santamarina-Fojo, S. in: PubMed | Google Scholar

Published February 1, 1996 - More info

Published in Volume 97, Issue 3 on February 1, 1996
J Clin Invest. 1996;97(3):799–805. https://doi.org/10.1172/JCI118479.
© 1996 The American Society for Clinical Investigation
Published February 1, 1996 - Version history
View PDF
Abstract

Hepatic lipase (HL) is an endothelial-bound lipolytic enzyme which functions as a phospholipase as well as a triacylglycerol hydrolase and is necessary for the metabolism of IDL and HDL. To evaluate the feasibility of replacing an enzyme whose in vivo physiologic function depends on its localization on the vascular endothelium, we have infused recombinant replication-deficient adenovirus vectors expressing either human HL (HL-rAdV; n = 7) or luciferase cDNA (Lucif-rAdV; n = 4) into HL-deficient mice with pretreatment plasma cholesterol, phospholipid, and HDL cholesterol values of 176 +/- 9, 314 +/- 12, and 129 +/- 9, respectively. After infusion of HL-rAdV, HL could be detected in the postheparin plasma of HL-deficient mice by immunoblotting and postheparin plasma HL activities were 25,700 +/- 4,810 and 1,510 +/- 688 nmol/min/ml on days 5 and 15, respectively. Unlike the mouse HL, 97% of the newly synthesized human HL was heparin releasable, indicating that the human enzyme was virtually totally bound to the mouse vascular endothelium. Infusion of HL-rAdV in HL-deficient mice was associated with a 50-80% decrease in total cholesterol, triglyceride, phospholipids, cholesteryl ester, and HDL cholesterol (P < 0.001) as well as normalization of the plasma fast protein liquid chromatography lipoprotein profile by day 8. These studies demonstrate successful expression and delivery of a lipolytic enzyme to the vascular endothelium for ultimate correction of the HL gene defect in HL-deficient mice and indicate that recombinant adenovirus vectors may be useful in the replacement of endothelial-bound lipolytic enzymes in human lipolytic deficiency states.

Version history
  • Version 1 (February 1, 1996): No description
Advertisement
Advertisement