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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 4

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VLDL turnover studies in hLpLGPI/LpL1 mice. (a and b) Plasma VLDL cleara...
VLDL turnover studies in hLpLGPI/LpL1 mice. (a and b) Plasma VLDL clearance without (a) and after heparin injection (b) in LpL1 and hLpLGPI/LpL1 mice. [3H]palmitate-labeled VLDL produced in LpL1 mice was intravenously injected into LpL1 and hLpLGPI/LpL1 male mice, and plasma was obtained by retro-orbital bleeds. The plasma count at 0.5 min after injection was considered as the injected dose. Plasma VLDL clearance did not differ between LpL1 (open circles, n = 9) and hLpLGPI/LpL1 mice (filled circles, n = 8). For FCR, LpL1 versus hLpLGPI/LpL1 = 13.7 ± 6.6 versus 12.1 ± 4.4 pools/h. Heparinized hLpLGPI/LpL1 mice (filled circles, n = 10) had faster clearance of radiolabeled VLDL than LpL1 mice (open circles, n = 9). For FCR, LpL1 versus hLpLGPI/LpL1 15.3 ± 6.0 versus 24.3 ± 7.4 pools/h, P < 0.02. (c and d) Heart uptake of VLDL-TG (c) and after heparin (d) from LpL1 and hLpLGPI/LpL1 mice. (c) Hearts of hLpLGPI/LpL1 (black bar, n = 8) mice had 54% more VLDL-TG uptake than control (LpL1) hearts (white bar, n = 9). LpL1 versus hLpLGPI/LpL1 = 0.016 ± 0.004 versus 0.025 ± 0.009 (heart dpm/injected dpm). (d) In the presence of heparin, hLpLGPI/LpL1 mice (black bar, n = 10) had 26% more VLDL-TG uptake in the hearts compared with control LpL1 mice (white bar, n = 9). LpL1 versus hLpLGPI/LpL1 = 0.015 ± 0.002 versus 0.019 ± 0.003 (heart dpm/injected dpm). Values are expressed as means ± SD. *P < 0.05; **P < 0.01.
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