Abstract
The apo B gene is expressed in the human heart and in the hearts of human apo B transgenic mice generated with large genomic clones spanning the human apo B gene. [35S]Methionine metabolic labeling experiments demonstrated that apo B100-containing lipoproteins are secreted by human heart tissue and by human apo B transgenic and nontransgenic mouse heart tissue. Density gradient analysis revealed that most of the secreted heart lipoproteins were LDLs, even when the labeling experiments were performed in the presence of tetrahydrolipstatin, an inhibitor of lipoprotein lipase. Western blots with a microsomal triglyceride transfer protein) (MTP)-specific antiserum demonstrated that the microsomes of the heart contain the 97-kD subunit of MTP (the subunit involved in the transfer of lipids and assembly of lipoproteins). Metabolic labeling of mouse heart tissue in the presence of BMS-192951, an MTP inhibitor, abolished lipoprotein secretion by the heart but resulted in the secretion of two apo B proteolytic fragments (80 and 120 kD), which were found in the bottom fraction of the density gradient. These studies reveal that the heart, and not just the liver and intestine, secretes apo B-containing lipoproteins. We speculate that lipoprotein secretion by the heart represents a mechanism for removing excess lipids from the heart.
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Selected References
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- Blanchette-Mackie E. J., Masuno H., Dwyer N. K., Olivecrona T., Scow R. O. Lipoprotein lipase in myocytes and capillary endothelium of heart: immunocytochemical study. Am J Physiol. 1989 Jun;256(6 Pt 1):E818–E828. doi: 10.1152/ajpendo.1989.256.6.E818. [DOI] [PubMed] [Google Scholar]
- Borén J., Rustaeus S., Olofsson S. O. Studies on the assembly of apolipoprotein B-100- and B-48-containing very low density lipoproteins in McA-RH7777 cells. J Biol Chem. 1994 Oct 14;269(41):25879–25888. [PubMed] [Google Scholar]
- Callow M. J., Stoltzfus L. J., Lawn R. M., Rubin E. M. Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2130–2134. doi: 10.1073/pnas.91.6.2130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dhalla N. S., Elimban V., Rupp H. Paradoxical role of lipid metabolism in heart function and dysfunction. Mol Cell Biochem. 1992 Oct 21;116(1-2):3–9. doi: 10.1007/978-1-4615-3514-0_1. [DOI] [PubMed] [Google Scholar]
- Du E. Z., Wang S. L., Kayden H. J., Sokol R., Curtiss L. K., Davis R. A. Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in abetalipoproteinemia. J Lipid Res. 1996 Jun;37(6):1309–1315. [PubMed] [Google Scholar]
- Farese R. V., Jr, Cases S., Ruland S. L., Kayden H. J., Wong J. S., Young S. G., Hamilton R. L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice. J Lipid Res. 1996 Feb;37(2):347–360. [PubMed] [Google Scholar]
- Gordon D. A., Jamil H., Gregg R. E., Olofsson S. O., Borén J. Inhibition of the microsomal triglyceride transfer protein blocks the first step of apolipoprotein B lipoprotein assembly but not the addition of bulk core lipids in the second step. J Biol Chem. 1996 Dec 20;271(51):33047–33053. doi: 10.1074/jbc.271.51.33047. [DOI] [PubMed] [Google Scholar]
- Gordon D. A. Recent advances in elucidating the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein assembly. Curr Opin Lipidol. 1997 Jun;8(3):131–137. doi: 10.1097/00041433-199706000-00002. [DOI] [PubMed] [Google Scholar]
- Hadjiagapiou C., Giannoni F., Funahashi T., Skarosi S. F., Davidson N. O. Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein. Nucleic Acids Res. 1994 May 25;22(10):1874–1879. doi: 10.1093/nar/22.10.1874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herscovitz H., Kritis A., Talianidis I., Zanni E., Zannis V., Small D. M. Murine mammary-derived cells secrete the N-terminal 41% of human apolipoprotein B on high density lipoprotein-sized lipoproteins containing a triacylglycerol-rich core. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):659–663. doi: 10.1073/pnas.92.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herz J., Willnow T. E., Farese R. V., Jr Cholesterol, hedgehog and embryogenesis. Nat Genet. 1997 Feb;15(2):123–124. doi: 10.1038/ng0297-123. [DOI] [PubMed] [Google Scholar]
- Linton M. F., Farese R. V., Jr, Chiesa G., Grass D. S., Chin P., Hammer R. E., Hobbs H. H., Young S. G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). J Clin Invest. 1993 Dec;92(6):3029–3037. doi: 10.1172/JCI116927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lookene A., Skottova N., Olivecrona G. Interactions of lipoprotein lipase with the active-site inhibitor tetrahydrolipstatin (Orlistat). Eur J Biochem. 1994 Jun 1;222(2):395–403. doi: 10.1111/j.1432-1033.1994.tb18878.x. [DOI] [PubMed] [Google Scholar]
- Peterson J., Bihain B. E., Bengtsson-Olivecrona G., Deckelbaum R. J., Carpentier Y. A., Olivecrona T. Fatty acid control of lipoprotein lipase: a link between energy metabolism and lipid transport. Proc Natl Acad Sci U S A. 1990 Feb;87(3):909–913. doi: 10.1073/pnas.87.3.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sack M. N., Rader T. A., Park S., Bastin J., McCune S. A., Kelly D. P. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation. 1996 Dec 1;94(11):2837–2842. doi: 10.1161/01.cir.94.11.2837. [DOI] [PubMed] [Google Scholar]
- Severson D. L., Lee M., Carroll R. Secretion of lipoprotein lipase from myocardial cells isolated from adult rat hearts. Mol Cell Biochem. 1988 Jan;79(1):17–24. doi: 10.1007/BF00229393. [DOI] [PubMed] [Google Scholar]
- Wetterau J. R., Aggerbeck L. P., Bouma M. E., Eisenberg C., Munck A., Hermier M., Schmitz J., Gay G., Rader D. J., Gregg R. E. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science. 1992 Nov 6;258(5084):999–1001. doi: 10.1126/science.1439810. [DOI] [PubMed] [Google Scholar]
- Wettesten M., Boström K., Bondjers G., Jarfeldt M., Norfeldt P. I., Carrella M., Wiklund O., Borén J., Olofsson S. O. Pulse-chase studies of the synthesis of apolipoprotein B in a human hepatoma cell line, Hep G2. Eur J Biochem. 1985 Jun 18;149(3):461–466. doi: 10.1111/j.1432-1033.1985.tb08947.x. [DOI] [PubMed] [Google Scholar]
- Wyne K. L., Pathak K., Seabra M. C., Hobbs H. H. Expression of the VLDL receptor in endothelial cells. Arterioscler Thromb Vasc Biol. 1996 Mar;16(3):407–415. doi: 10.1161/01.atv.16.3.407. [DOI] [PubMed] [Google Scholar]
- van der Vusse G. J., Glatz J. F., Stam H. C., Reneman R. S. Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev. 1992 Oct;72(4):881–940. doi: 10.1152/physrev.1992.72.4.881. [DOI] [PubMed] [Google Scholar]