Abstract
Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of 125I-labeled LDL, LDL transport across the monolayers was unchanged; but, at all concentrations of LDL tested (1-100 micrograms), LDL retention by the monolayers increased more than fourfold. 125I-labeled LDL binding to extracellular matrix increased when LPL was added directly to the matrix or was added to the basolateral side of the endothelial cell monolayers. Increased LDL binding required the presence of LPL and was not associated with LDL aggregation. LPL also increased VLDL, but not HDL, retention. Monoclonal anti-LPL IgG decreased both VLDL and LDL retention in the presence of LPL. Lipoprotein transport across the monolayers increased during hydrolysis of VLDL triglyceride (TG). In the presence of LPL and VLDL, VLDL transport across the monolayers increased 18% and LDL transport increased 37%. High molar concentrations of oleic acid to bovine serum albumin (3:1) in the medium increased VLDL transport approximately 30%. LDL transport increased 42% when oleic acid was added to the media. Therefore, LPL primarily increased retention of LDL and VLDL. A less remarkable increase in lipoprotein transport was found during hydrolysis of TG-containing lipoproteins. We hypothesize that LPL-mediated VLDL and LDL retention within the arterial wall potentiates conversion of these lipoproteins to more atherogenic forms.
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- Basu S. K., Brown M. S., Ho Y. K., Goldstein J. L. Degradation of low density lipoprotein . dextran sulfate complexes associated with deposition of cholesteryl esters in mouse macrophages. J Biol Chem. 1979 Aug 10;254(15):7141–7146. [PubMed] [Google Scholar]
- Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
- Bratzler R. L., Chisolm G. M., Colton C. K., Smith K. A., Lees R. S. The distribution of labeled low-density lipoproteins across the rabbit thoracic aorta in vivo. Atherosclerosis. 1977 Nov;28(3):289–307. doi: 10.1016/0021-9150(77)90177-0. [DOI] [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. doi: 10.1146/annurev.bi.52.070183.001255. [DOI] [PubMed] [Google Scholar]
- Chait A., Iverius P. H., Brunzell J. D. Lipoprotein lipase secretion by human monocyte-derived macrophages. J Clin Invest. 1982 Feb;69(2):490–493. doi: 10.1172/JCI110473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chajek-Shaul T., Friedman G., Bengtsson-Olivecrona G., Vlodavsky I., Bar-Shavit R. Interaction of lipoprotein lipase with subendothelial extracellular matrix. Biochim Biophys Acta. 1990 Feb 6;1042(2):168–175. doi: 10.1016/0005-2760(90)90003-g. [DOI] [PubMed] [Google Scholar]
- Cheng C. F., Oosta G. M., Bensadoun A., Rosenberg R. D. Binding of lipoprotein lipase to endothelial cells in culture. J Biol Chem. 1981 Dec 25;256(24):12893–12898. [PubMed] [Google Scholar]
- Chung B. H., Segrest J. P., Smith K., Griffin F. M., Brouillette C. G. Lipolytic surface remnants of triglyceride-rich lipoproteins are cytotoxic to macrophages but not in the presence of high density lipoprotein. A possible mechanism of atherogenesis? J Clin Invest. 1989 Apr;83(4):1363–1374. doi: 10.1172/JCI114024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eckel R. H. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med. 1989 Apr 20;320(16):1060–1068. doi: 10.1056/NEJM198904203201607. [DOI] [PubMed] [Google Scholar]
- Falcone D. J., Mated N., Shio H., Minick C. R., Fowler S. D. Lipoprotein-heparin-fibronectin-denatured collagen complexes enhance cholesteryl ester accumulation in macrophages. J Cell Biol. 1984 Oct;99(4 Pt 1):1266–1274. doi: 10.1083/jcb.99.4.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fogelman A. M., Shechter I., Seager J., Hokom M., Child J. S., Edwards P. A. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2214–2218. doi: 10.1073/pnas.77.4.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerrity R. G. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981 May;103(2):181–190. [PMC free article] [PubMed] [Google Scholar]
- Goldberg I. J., Blaner W. S., Vanni T. M., Moukides M., Ramakrishnan R. Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys. J Clin Invest. 1990 Aug;86(2):463–473. doi: 10.1172/JCI114732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldberg I. J., Handley D. A., Vanni T., Paterniti J. R., Jr, Cornicelli J. A. Membrane-bound lipoprotein lipase on human monocyte-derived macrophages: localization by immunocolloidal gold technique. Biochim Biophys Acta. 1988 Apr 15;959(3):220–228. doi: 10.1016/0005-2760(88)90194-4. [DOI] [PubMed] [Google Scholar]
- Goldberg I. J., Kandel J. J., Blum C. B., Ginsberg H. N. Association of plasma lipoproteins with postheparin lipase activities. J Clin Invest. 1986 Dec;78(6):1523–1528. doi: 10.1172/JCI112744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldberg I. J., Le N. A., Ginsberg H. N., Krauss R. M., Lindgren F. T. Lipoprotein metabolism during acute inhibition of lipoprotein lipase in the cynomolgus monkey. J Clin Invest. 1988 Feb;81(2):561–568. doi: 10.1172/JCI113354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein J. L., Ho Y. K., Brown M. S., Innerarity T. L., Mahley R. W. Cholesteryl ester accumulation in macrophages resulting from receptor-mediated uptake and degradation of hypercholesterolemic canine beta-very low density lipoproteins. J Biol Chem. 1980 Mar 10;255(5):1839–1848. [PubMed] [Google Scholar]
- HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hennig B., Shasby D. M., Fulton A. B., Spector A. A. Exposure to free fatty acid increases the transfer of albumin across cultured endothelial monolayers. Arteriosclerosis. 1984 Sep-Oct;4(5):489–497. doi: 10.1161/01.atv.4.5.489. [DOI] [PubMed] [Google Scholar]
- Hoff H. F., Heideman C. L., Jackson R. L., Bayardo R. J., Kim H. S., Gotto A. M., Jr Localization patterns of plasma apolipoproteins in human atherosclerotic lesions. Circ Res. 1975 Jul;37(1):72–79. doi: 10.1161/01.res.37.1.72. [DOI] [PubMed] [Google Scholar]
- Iverius P. H. The interaction between human plasma lipoproteins and connective tissue glycosaminoglycans. J Biol Chem. 1972 Apr 25;247(8):2607–2613. [PubMed] [Google Scholar]
- Jackson R. L., Socorro L., Fletcher G. M., Cardin A. D. Heparin binding to lipoprotein lipase and low density lipoproteins. FEBS Lett. 1985 Oct 14;190(2):297–300. doi: 10.1016/0014-5793(85)81304-1. [DOI] [PubMed] [Google Scholar]
- Jonasson L., Bondjers G., Hansson G. K. Lipoprotein lipase in atherosclerosis: its presence in smooth muscle cells and absence from macrophages. J Lipid Res. 1987 Apr;28(4):437–445. [PubMed] [Google Scholar]
- Kekki M. Lipoprotein-lipase action determining plasma high density lipoprotein cholesterol level in adult normolipaemics. Atherosclerosis. 1980 Sep;37(1):143–150. doi: 10.1016/0021-9150(80)90102-1. [DOI] [PubMed] [Google Scholar]
- Khoo J. C., Mahoney E. M., Witztum J. L. Secretion of lipoprotein lipase by macrophages in culture. J Biol Chem. 1981 Jul 25;256(14):7105–7108. [PubMed] [Google Scholar]
- Kirchgessner T. G., Svenson K. L., Lusis A. J., Schotz M. C. The sequence of cDNA encoding lipoprotein lipase. A member of a lipase gene family. J Biol Chem. 1987 Jun 25;262(18):8463–8466. [PubMed] [Google Scholar]
- Lindqvist P., Ostlund-Lindqvist A. M., Witztum J. L., Steinberg D., Little J. A. The role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins by macrophages. J Biol Chem. 1983 Aug 10;258(15):9086–9092. [PubMed] [Google Scholar]
- Lynch J. J., Ferro T. J., Blumenstock F. A., Brockenauer A. M., Malik A. B. Increased endothelial albumin permeability mediated by protein kinase C activation. J Clin Invest. 1990 Jun;85(6):1991–1998. doi: 10.1172/JCI114663. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radhakrishnamurthy B., Srinivasan S. R., Vijayagopal P., Berenson G. S. Arterial wall proteoglycans--biological properties related to pathogenesis of atherosclerosis. Eur Heart J. 1990 Aug;11 (Suppl E):148–157. doi: 10.1093/eurheartj/11.suppl_e.148. [DOI] [PubMed] [Google Scholar]
- Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
- Saxena U., Klein M. G., Goldberg I. J. Transport of lipoprotein lipase across endothelial cells. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2254–2258. doi: 10.1073/pnas.88.6.2254. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saxena U., Witte L. D., Goldberg I. J. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids. J Biol Chem. 1989 Mar 15;264(8):4349–4355. [PubMed] [Google Scholar]
- Schwenke D. C., Carew T. E. Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries. Arteriosclerosis. 1989 Nov-Dec;9(6):908–918. doi: 10.1161/01.atv.9.6.908. [DOI] [PubMed] [Google Scholar]
- Shasby D. M., Shasby S. S. Active transendothelial transport of albumin. Interstitium to lumen. Circ Res. 1985 Dec;57(6):903–908. doi: 10.1161/01.res.57.6.903. [DOI] [PubMed] [Google Scholar]
- Sloop C. H., Dory L., Roheim P. S. Interstitial fluid lipoproteins. J Lipid Res. 1987 Mar;28(3):225–237. [PubMed] [Google Scholar]
- Steinberg D. Lipoproteins and atherosclerosis. A look back and a look ahead. Arteriosclerosis. 1983 Jul-Aug;3(4):283–301. doi: 10.1161/01.atv.3.4.283. [DOI] [PubMed] [Google Scholar]
- Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
- Suits A. G., Chait A., Aviram M., Heinecke J. W. Phagocytosis of aggregated lipoprotein by macrophages: low density lipoprotein receptor-dependent foam-cell formation. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2713–2717. doi: 10.1073/pnas.86.8.2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Traber M. G., Kayden H. J. Low density lipoprotein receptor activity in human monocyte-derived macrophages and its relation to atheromatous lesions. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5466–5470. doi: 10.1073/pnas.77.9.5466. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weisgraber K. H., Rall S. C., Jr Human apolipoprotein B-100 heparin-binding sites. J Biol Chem. 1987 Aug 15;262(23):11097–11103. [PubMed] [Google Scholar]
- Ylä-Herttuala S., Lipton B. A., Rosenfeld M. E., Goldberg I. J., Steinberg D., Witztum J. L. Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10143–10147. doi: 10.1073/pnas.88.22.10143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zilversmit D. B. Atherogenesis: a postprandial phenomenon. Circulation. 1979 Sep;60(3):473–485. doi: 10.1161/01.cir.60.3.473. [DOI] [PubMed] [Google Scholar]
- el Touny S., Khan W., Hannun Y. Regulation of platelet protein kinase C by oleic acid. Kinetic analysis of allosteric regulation and effects on autophosphorylation, phorbol ester binding, and susceptibility to inhibition. J Biol Chem. 1990 Sep 25;265(27):16437–16443. [PubMed] [Google Scholar]