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Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy
Hiroaki Yagyu, … , Shunichi Homma, Ira J. Goldberg
Hiroaki Yagyu, … , Shunichi Homma, Ira J. Goldberg
Published February 1, 2003
Citation Information: J Clin Invest. 2003;111(3):419-426. https://doi.org/10.1172/JCI16751.
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Article Cardiology

Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy

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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 α-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

Hiroaki Yagyu, Guangping Chen, Masayoshi Yokoyama, Kumiko Hirata, Ayanna Augustus, Yuko Kako, Toru Seo, Yunying Hu, E. Peer Lutz, Martin Merkel, André Bensadoun, Shunichi Homma, Ira J. Goldberg

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Figure 6

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(a and b) LpL immunofluorescence in the hearts. An mAb was used to detec...
(a and b) LpL immunofluorescence in the hearts. An mAb was used to detect hLpL in hearts. In mice with transgenic expression of normal hLpL in the hearts on the homozygous LpL knockout background (He-LpL/LpL0) (28), hLpL was found in the cytoplasm and at the membrane. Hearts from hLpLGPI/LpL1 mice had intense staining for LpL on the surface of cardiomyocytes. In a, intensity of red staining is amplified tenfold compared with b. (c and d) Myocardial lipid accumulation in 24 h–fasted hLpLGPI/LpL1 mice. Oil red O staining shows an abundance of neutral lipid droplets within the cardiomyocytes of hLpLGPI/LpL1 (d) mice compared with LpL1 (c) mice. ×400. (e and f) Electron microscopy. Ultrastructure of LpL1 mouse myocardial tissues exhibited normal morphological features with well-organized myofilaments and mitochondria (e). T tubules are not visible. The hLpLGPI/LpL1 myocytes appeared severely distorted due to more mitochondria, irregular Z band of myofibrils, and dilated T tubules (f). (g) Northern blot analysis. Ten micrograms of total RNA were isolated from heart and subjected to Northern blot analysis using a part of cDNA encoding PPARα, CPT-1, ACO, ANF, and GLUT4 as probes. GAPDH is shown as a control for loading.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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