Abstract
The vascular endothelium can be regarded as a widely distributed organ, interposed between the intravascular and extravascular spaces, with a pluripotent function in the regulation of capillary diameter, vascular homeostasis, lipoprotein metabolism and the vascular response to injury. In the basal physiological state these processes provide a non-thrombotic, non-inflammatory vascular lining preventing uncontrolled inflammation and coagulation. Endothelial cells respond to potential harmful conditions (mechanical stress, anoxia, ischemia and oxidative stress) and a variety of hormones and vasoactive mediators by inducing coagulation and production of inflammatory mediators through the production of ‘bioactive’ lipids. Although the number of studies in isolated myocardial endothelial cells is limited, from the presumed metabolic analogy with endothelial cells isolated (and cultured) from other organs, one may conclude that the bioactive lipids include oxygenated arachidonate metabolites (eicosanoids) and the platelet activating factor (1--O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; PAF). All aspects of lipid metabolism, related to the production of eicosanoids and PAF, are present within myocardial endothelial cells. There is uptake and incorporation of fatty acids by endothelial cells and liberation from endogenous triacylglycerol and (membrane) phospholipid stores by (phospho)lipases. Endothelial cells oxidize fatty acids in a carnitine-dependent, mitochondrial, pathway. Endothelial cells actively interact with high density lipoprotein (HDL) and low density lipoprotein (LDL) leading to uptake of cholesterol(esters) that undergo intracellular hydrolysis, and re-esterification to phosphoand neutral lipids, and leaving the LDL-particle modified in a way that makes them bind to the scavenger receptor on macrophages. Extravascular triacylglycerols in lipoproteins (very low density lipoprotein (VLDL), chylomicrons) are handled by endothelial cell lipoprotein lipase, providing substrate fatty acids for the underlying muscle tissue. Eicosanoid production from (membrane)phospholipids and PAF synthesis from alkylphospholipids are tightly coupled and interrelated to the flow of arachidonic acid between cellular lipid pools. (Mol Cell Biochem116: 171–179, 1992)
Similar content being viewed by others
References
Jaffe EA: Cell biology of endothelial cells. Hum Pathol 18: 234–239, 1987
Vane JR, Gryglewski RJ, Botting RM: The endothelial cell as a metabolic and endocrine organ. TIPS 8: 491–496, 1987
Whatley RE, Zimmerman GA, McIntyre TM, Prescot SM: Lipid metabolism and signal transduction in endothelial cells. Prog Lipid Res 29: 45–63, 1990
Munro JM, Cotran RS: The pathogenesis of atherosclerosis; atherogenesis and inflammation. Lab Invest 58: 249–261, 1988
Gimbrone MA: Endothelial dysfunction and the pathogenesis of atherosclerosis. In: AM Gotto, LC Smith and B Allen (eds) Atherosclerosis V. Proceedings of the Fifth International Symposium. Springer Verlag, New York, Heidelberg, Berlin, 1979, pp 415–425
Reidy MA: Biology of disease. A reassesment of endothelial injury and arterial lesion formation. Lab Invest 53: 513–520, 1985
Bassinthwaighte JB, Noodleman L, Van der Vusse G, Glatz JFC: Modeling of palmitate transport in the heart. Mol Cell Biochem 88: 51–59, 1989
Scow RO, Blanchette-Mackie EJ, Smith LC: Transport of lipids across capillary endothelium. Fed Proc 39: 2610–2617, 1980
Cryer A: The role of the endothelium in myocardial lipoprotein dynamics. Mol Cell Biochem 88: 7–16, 1988
Hennig RB, Shasby DM, Spector AA: Exposure to fatty acids increases human low density lipoprotein transfer across cultured endothelial monolayers. Cire Res 57: 761–786, 1985
Hiilsmann WC, Dubelaar ML: Lipoprotein lipases and stress hormones: Studies with glucocorticoids and choleratoxin. Biochim Biophys Acta 875: 69–75, 1986
Stein O, Stein Y: Bovine aortic endothelial cells display macrophage-like properties towards125I-labelled low density lipoprotein. Biochim Biophys Acta 620: 631–635, 1980
Tanimura N, Asada Y, Hayashi T, Kisanuki A, Sumiyoshi A: Aortic endothelial cell damage induced by ß-VLDL and macrophages in vitro. Atherosclerosis 85: 161–167, 1990
Baker DP, Van Lenten BJ, Fogelman AM, Edwards PA, Kean C, Berliner JA: LDL, scavenger, and ß-VLDL receptors on aortic endothelial cells. Arteriosclerosis 4: 248–255, 1984
Fielding CJ: The endothelium, triglyceride-rich lipoproteins and atherosclerosis. Insights from cell biology and lipid metabolism. Diabetes 30 (suppl 2): 19–23, 1981
Tauber JP, Goldminz D, Gospodarowicz D: Up-regulation in vascular endothelial cells of binding sites of high density lipoprotein induced by 25-hydroxycholesterol. Eur J Biochem 119: 327–339, 1981
Savion N, Kotev-Emeth S: Cholesterol efflux from and high density lipoprotein binding to cultured bovine vascular endothelial cells are higher than with vascular smooth muscle cells. Eur J Biochem 183: 363–370, 1989
Palade GE: Transport in quanta across endothelium of blood capillaries. Anal Rev 136: 254–262, 1960
Williams SK: Vesicular transport of proteins by capillary endothelium. In: AL Copley, GV Seaman (eds) Surface phenomena in hemorheology. Their theoretical, experimental and clinical aspects. Vol 416 NY Acad Sci, New York, 1985, pp 457–465
Constantidines P: The arterial endothelium. Present state of knowledge. Wien Klin Wochenschr 94: 627–630, 1982
Hendriksen T, Mahoney EM, Steinberg D: Enhanced macrophage degradation of low density lipoproteins previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoprotein. Proc Nall Acad Sci USA 78: 6499–6503, 1981
Parthasarathy S, Printz DJ, Boyd D, Joy L, Steinberg D: Macrophage oxidation of low density lipoprotein generates a modified from recognized by the scavenger receptor. Arteriosclerosis 6: 505–510, 1986
Cathcart MK, Morel D, Chisolm GM III: Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J Leukocyte Biol 38: 341–350, 1985
Parthasarathy S, Wieland E, Steinberg D: A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci USA 86: 1046–1050, 1989
Quinn MT, Parthasarathy S, Fong LG, Steinberg D: Oxidatively modified low density lipoproteins: A potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA 84: 2995–2998, 1987
Horrigan S, Campbell JH, Campbell GR: Effect of endothelium on ß-VLDL metabolism by cultured smooth muscle cells of differing phenotype. Atherosclerosis 71: 57–69, 1988
Spector AA, Kaduce TL, Hoak JC, Fry GL: Utilization of arachidonic and linoleic acids by cultured human endothelial cells. J Clin Invest 68: 1003–1011, 1981
Spector AA, Mathur SN, Kaduce TL, Hyman BT: Lipid nutrition and metabolism of cultured mammalian cells. Prog Lipid Res 19: 155–186, 1981
Hoak JC, Czervionke RL, Lewis LJ: Uptake and utilization of free fatty acids (FFA) by human endothelial cells. Thromb Res 4: 879–883, 1974
Spector AA, Hoak JC, Fry GL, Stoll LL, Tanke CT, Kaduce TL: Essential fatty acid availability and prostacyclin production by cultured human endothelial cells. Prog Lip Res 20: 471–477, 1981
Roux FS, Mokni R, Hughes CC, Clouet PM, Lefauconnier JM, Bourre JM: Lipid synthesis by rat brain microvessel endothelial cells in tissue culture. J Neuropathol Exp Neurol 48: 437–447, 1989
Fielding PE, Vlodavsky I, Gospodarowicz D, Fielding CJ: Effect of contact inhibition on the regulation of cholesterol metabolism in cultured vascular endothelial cells. J Biol Chem 244: 749–755, 1979
Denning GM, Figard PH, Kaduce TL, Spector AA: Role of triglycerides in endothelial cell arachidonic acid metabolism. J Lipid Res 24: 993–1001, 1983
Rosenthal MD: Fatty acid metabolism of isolated mammalian cells. Prog Lipid Res 26: 87–124, 1987
Neufeld EJ, Wilson DB, Sprecher H, Majerus PW: High affinity esterification of eicosanoid precursor fatty acids by platelets. J Clin Invest 72: 214–220, 1983
Lands WEM, Crawford CG: Biosynthesis of cell components. In: A Martonosi (ed.) The enzymes of Biological Membranes Vol 2. Plenum Press, New York, 1976, pp 3–85
Bell RM, Coleman RA: Enzymes of triacylglycerol formation in mammals. In: PD Boyer (ed.) The enzymes. Acad Press Inc Vol XVI, 1983, pp 87–111
Huang CF, Chabot MC: Phorbol diesters stimulate the accumulation of phosphatidate, phosphatidylethanol and diacylglycerol in three cell types. Evidence for the indirect formation of phosphatidylcholine-derived diacylglycerol by a phospholipase D pathway and direct formation of diacylglycerol by a phospholipase C pathway. J Biol Chem 265: 14858–14863, 1990
Martin TW: Formation of diacylglycerol by a phospholipase-Dphosphatidate phosphatase pathway specific for phosphatidylcholine in endothelial cells. Biochim Biophys Acta 962: 282–296, 1988
Exton JH: Signaling through phosphatidylcholine breakdown. J Biol Chem 265: 1–4, 1990
Wey HE, Jakubowski JA, Deykin D: Incorporation and redistribution of arachidonic acid in diacyl and ether phospholipids of bovine aortic endothelial cells. Biochim Biophys Acta 878: 380–386, 1986
Kolesnick RN, Paley AE: 1,2-Diacylglycerols and phorbolesters stimulate phosphatidylcholine metabolism in GH3 pituitary cells. Evidence for separate mechanisms of action. J Biol Chem 262: 9204–9210, 1987
Daniel LW, Waite M, Wykle RL: A novel mechanism of diglyceride formation. 12-O-tetradecanoylphorbol-13-acetate stimulates the cyclic breakdown and resynthesis of phosphatidylcholine. J Biol Chem 261: 9128–9132, 1986
Fuse I, Tai HH: Regulation of arachidonate release by G-proteins and protein kinase C in human platelets. Adv Prostaglandin Thromboxane Leukotriene Res 19: 574–579, 1989
Tsai PY, Geyer RP: Fatty acid synthesis and metabolism of phospholipid acyl groups in strain L mouse fibroblasts. Biochim Biophys Acta 489: 381–389, 1977
Tsai PY, Geyer RP: Effect of exogenous fatty acids on the retention of phospholipid acyl groups by mouse L fibroblasts. Biochim Biophys Acta 528: 344–354, 1978
Hennig B, Shasby DM, Fulton AB, Spector AA: Exposure to free fatty acid increases the transfer of albumin across cultured endothelial monolayers. Arteriosclerosis 4: 489–497, 1984
Linssen MCJG, Vork MM, De Jong YF, Glatz JFC, Van der Vusse GJ: Fatty acid oxydation capacity and fatty acid binding protein content of different cell types isolated from rat heart. Mol Cell Biochem 98: 19–25, 1990
Tsai PY, Geyer RP: Stimulating effect of hydrocortisone on the catabolism of endogenous fatty acyl groups by fatty acid-supplemented mouse L fibroblasts. J Biol Chem 253: 5087–5089, 1978
Stam H, Hülsmann WC: Regulation of lipases involved in the supply of substrate fatty acids for the heart. Eur Heart J 6: 158–167, 1985
Stam H, Hülsmann WC, Jongkind JF, Van der Kraay AMM, Koster JF: Endothelial lesions, dietary composition and lipid peroxidation. Eicosanoids 2: 1–14, 1989
Spahr R, Krützfeldt A, Mertens S, Siegmund B, Piper HM: Fatty acids are not an important fuel for coronary microvascular endothelial cells. Mol Cell Biochem 88: 59–64, 1989
Hülsmann WC, Dubelaar ML: Aspects of fatty acid metabolism in vascular endothelial cells. Biochimie 70: 681–686, 1988
Van Hinsberg VWM, Emeis JJ, Havekes L: Interaction of lipoproteins with cultured endothelial cells. In: The Endothelial Cells -a pluripotent control of the vessel wall. 1st Int Endothelial Cell Symp of the ETCS, Paris, Karger, Basel, 1982, pp99–112
Leighton B, Curi R, Hussein A, Newsholme EA: Maximum activities of some key enzymes of glycolysis, glutaminolysis, Krebs cycle and fatty acid utilization in bovine pulmonary endothelial cells. FEBS Lett 225: 93–96, 1987
Chace KV, Odessey R: The utilization by rabbit aorta of carbodydrates, fatty acids, ketone bodies and amino acids as substrates for energy production. Circ Res 48: 850–858, 1981
Kohane D, Cunningham L, Cohen R, Brecher P: Fatty acid utilization by vascular endothelium (Abstract). J Cell Biol 107: 863a,1988
Mertens S, Noll T, Spahr R, Krützfeldt A, Piper HM: Energetic response of coronary endothelial cells to hypoxia. Am J Physiol 258: H689-H694, 1990
Krützfeldt A, Spahr R, Mertens S, Siegmund B, Piper HM: Metabolism of exogenous substrates by coronary endothelial cells in culture. J Mol Cell Cardiol 22: 1393–1404, 1990
McKenzie CG, McKenzie JB, Reiss OK: Increase in cell lipid and cytoplasmatic particles in mammalian cells cultured at reduced pH. J Lipid Res 8: 642–645, 1967
Van der Vusse GJ, Roemen THM, Prinzen FW, Coumans WA, Reneman RS: Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischeemic conditions. Circ Res 50: 538–546, 1982
Chien KR, Han A, Sen A, Buja LM, Willerson JT: Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Circ Res 54: 313–322, 1984
Figard PH, Hejlik DP, Kaduce TL, Stoll LL, Spector AA: Free fatty acid release from endothelial cells. J Lipid Res 27: 771–780, 1986
Ragab-Thomas JM, Hullin F, Chap H, Douste-Blazy L: Pathways of arachidonic acid liberation in thrombin and calciumionophore A23187 stimulated human endothelial cells: Respec tive roles of phospholipids and triacylglycerol and evidence for diacylglycerol formation from phosphatidylcholine. Biochim Biophys Acta 917: 388–397, 1987
Hong SL, McLaughin NJ, Tzeng CY, Patton G: Prostacyclin synthesis and deacylation of phospholipids in human endothelial cells: Comparison of thrombin, histamine and ionophore A23187. Thromb Res 38: 1–10, 1985
Bhagyalakshmi A, Frangos JA: Mechanism of shear-induced prostacyclin production in endothelial cells. Biochem Biophys Res Commun 158: 31–37, 1989
Schoonderwoerd K, Broekhoven-Schokker S, Hülsmann WC, Stam H: Involvement of lysosome-like particles in the metabolism of endogenous myocardial triglycerides during ischemia/ reperfusion. Uptake and degradation of triglycerides by lysosomes isolated from rat heart. Basic Res Cardiol 85: 153–163, 1990
Hong SL: Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical cord vein. Thromb Res 18: 787–795, 1980
Martin TW, Wysolmerski RB, Lagunoff D: Phosphatidylcholine metabolism in endothelial cells: Evidence for phospholipase A and a novel calcium-independent phospholipase C. Biochim Biophys Acta 917: 296–307, 1987
Irvine RF: How is the level of free arachidonic acid controlled in mammalian cells? Biochem J 204: 3–16, 1982
Pomerantz KB, Fleisher LN, Tall AR, Cannon PJ: Enrichment of endothelial cell arachidonate by lipid transfer from high density lipoproteins: Relationship to prostaglandin Iz synthesis. J Lipid Res 26: 1269–1276, 1985
Spector AA, Scanu HM, Kaduce TC: Effect of human plasma lipoproteins on prostacyclin production by cultured endothelial cells. J Lipid Res 26: 288–297, 1985
Hallam TJ, Jacob R, Merritt JE: Evidence that agonists stimulate bivalent — cation influx into human endothelial cells. Biochem J 255: 179–184, 1988
Burch RM: G protein regulation of phospholipase A2. Mol Neurobiol 3: 155–171, 1989
Irving HR, Exton JH: Phosphatidylcholine breakdown in rat liver plasma membranes. Roles of guanine nucleotides and PZpurinergic agonists. J Biol Chem 262: 3440–3443, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schoonderwoerd, K., Stam, H. Lipid metabolism of myocardial endothelial cells. Mol Cell Biochem 116, 171–179 (1992). https://doi.org/10.1007/BF01270585
Issue Date:
DOI: https://doi.org/10.1007/BF01270585