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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 Article has an altmetric score of 3

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 3

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LpL expression in plasma and hearts. (a) Postheparin plasma LpL activity...
LpL expression in plasma and hearts. (a) Postheparin plasma LpL activity. There was no difference in postheparin LpL activity between LpL1 and three lines of hLpLGPI/LpL1 mice. LpL1, n = 6; line 346, n = 3; line 357, n = 6; line 358, n = 2. (b) Heart LpL activity. Hearts from control and three lines of male transgenic animals were homogenized and assayed for LpL activity in triplicate. Homogenates of hearts of hLpLGPI/LpL1 mice (line 357, n = 3) had 3.8-fold more LpL activity than control LpL1 mice (n = 4). *P < 0.01. (c) Myocardial human LpL. Human LpL was differentiated from mouse LpL using an mAb against human LpL activity. All the additional LpL activity in hearts from hLpLGPI/LpL1 mice (line 357, n = 3) was inhibited by the Ab, and no inhibition was found when the Ab was added to homogenates from control LpL1 hearts (n = 4). The graph shows the amount of activity inhibited by the Ab. Values are expressed as means ± SD. *P < 0.01. (d) Northern blot analysis of hLpLGPI mouse tissue RNA. Ten micrograms of total heart RNA from male mice was subjected to Northern blot analysis. Probe is shown in Figure 1c. The hLpLGPI mRNA was detected only in the hearts. H, heart; M, skeletal muscle; A, adipose; Lu, lung; Li, liver; K, kidney; S, spleen. (e) Lipoprotein profiles of LpL1 and hLpLGPI/LpL1 mice. Cholesterol distribution for LpL1 mice is shown with open circles and hLpLGPI/LpL1 mice with filled circles.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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