Heparin in combination with endothelial cell growth factor (ECGF) affects physiological responses and growth of human umbilical vein endothelial cells (HUVEC). We have examined the effect of heparin, crude ECGF (endothelial cell growth supplement [ECGS]), or both on the basal and thrombin challenged output of metabolites by HUVEC. The supernatant and/or cell lysate was assayed for released prostacyclin, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor and thrombospondin. Heparin modified release of all these metabolites when in combination with ECGS, and in general these responses were the opposite of those generated by inflammatory mediators such as interleukin-1. It has been postulated that heparin acts by potentiating the effect of ECGF, but heparin inhibited thrombospondin release and enhanced that of von Willebrand factor in the absence of ECGS, while ECGS alone inhibited release of plasminogen activator inhibitor. Thus, under our experimental conditions it would appear that heparin and crude ECGF can affect HUVEC independently of one another.
References
1
Thornton SC,
Mueller SN,
Levine EM.
Human endothelial cells: use of heparin in cloning and long-term serial cultivation. Science 1983; 222: 623-625
4
Burgess WH,
Mehlman T,
Marshak DR,
Fraser BA,
Maciag T.
Structural evidence that endothelial cell growth factor p is the precursor of both endothelial cell growth factor a and acidic fibroblast growth factor. Proc Natl Acad Sci USA 1986; 83: 7216-7220
5
Barzu T,
Lormeau JC,
Petitou M,
Michelson S,
Choay J.
Heparin-derived oligosaccharides: affinity for acidic fibroblast growth factor and effect on its growth-promoting activity for human endothelial cells. J Cell Physiol 1989; 140: 538-548
10
Andoh K,
Petterson KS,
Filion-Myklebust C,
Prydz H.
Observations on the cell biology of tissue factor in endothelial cells. Thromb Haemostas 1990; 63: 298-302
11
Weksler BB.
Heparin and acidic fibroblast growth factor interact to decrease prostacyclin synthesis in human endothelial cells by affecting both prostacyclin H synthase and prostacyclin synthase. J Cell Physiol 1990; 142: 514-522
12
Boutherin-Falson O,
Blaes N.
Decreased prostacyclin production by human umbilical vein endothelial cells cultured with endothelial cell growth factor and heparin. Thromb Res 1989; 54: 487-492
17
McArthur MM,
MacGregor IR,
Prowse CV,
Hunter NR,
Dawes J,
Pepper DS.
The use of human endothelial cells cultured in flat wells and on microcarrier beads to assess tissue plasminogen activator and factor VIII related antigen release. Thromb Res 1986; 41: 581-587
18
Dawes J,
Clemetson KJ,
Gogstad GD,
McGregor J,
Clezardin P,
Prowse CV,
Pepper DS.
A radioimmunoassay for thrombospondin, used in a comparative study of thrombospondin, p-thromboglobulin and platelet factor 4 in healthy volunteers. Thromb Res 1983; 29: 569-581
19
Hasegawa N,
Yamamoto M,
Yamamoto K.
Stimulation of cell growth and inhibition of prostacyclin production by heparin in human umbilical vein endothelial cells. J Cell Physiol 1988; 137: 603-607
20
Itoh F,
Kaji T,
Hayakama Y,
Oguma Y,
Sakuragawa N.
Heparin enhances thrombin-stimulated prostacyclin I2 production by cultured endothelial cells. Thromb Res 1990; 57: 481-488
21
Ingerman-Wojenski CM,
Silver MJ.
Prostacyclin synthesis by endothelial cells from human umbilical veins: effect of cumulative population doublings. Prostaglandins 1988; 36: 127-137
22
Ristimaki A,
Ylikorkala O,
Viinikka L.
Effect of growth factors on human vascular endothelial cell prostacyclin production. Arteriosclerosis 1990; 10: 653-657
23
Hanss M,
Collen D.
Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: modulation by thrombin, endotoxin, and histamine. J Lab Clin Med 1987; 109: 97-104
24
Marsh NM,
Minter AJ,
Chesterman CN.
The effect of heparin and other glycosaminoglycans on levels of tissue plasminogen activator and plasminogen activator inhibitor in cultured human umbilical vein endothelial cells. Blood Coag Fibrin 1990; 1: 133-138
26
Gelehrter TD,
Sznycer-Laszuk R.
Thrombin induction of plasminogen-activator-inhibitor in cultured human endothelial cells. J Clin Invest 1986; 77: 165-169
28
Lyons-Giordano B,
Brinker JM,
Kefalides NA.
The effect of heparin on fibronectin and thrombospondin synthesis and mRNA levels in cultured human endothelial cells. Exp Cell Res 1990; 186: 39-46
29
Chesterman CN,
Ager A,
Gordon JL.
Regulation of prostaglandin production and ectoenzyme activities in cultured aortic endothelial cells. J Cell Physiol 1983; 116: 45-50
30
Tan EM,
Dodge GR,
Sorger T,
Kovalsky I,
Unger GA,
Yang L,
Levine EM,
Iozzo RV.
Modulation of extracellular matrix gene expression by heparin and endothelial cell growth factor in human smooth muscle cells. Lab Invest 1991; 64: 474-482
32
Mikhailides DP,
Barradas MA,
O’Donoghue S,
Dandona P.
Evidence for in vivo platelet activation following the injection of conventional unfractionated heparin. Platelets 1990; 1: 189-192
34
Albrightson CR,
Baenziger NL,
Needleman P.
Exaggerated human vascular cell prostaglandin biosynthesis mediated by monocytes: role of monokines and interleukin 1. J Immunol 1985; 135: 1872-1877
37
Bevilacqua MP,
Schleef RR,
Gimbrone Jr MA,
Loskutoff DJ.
Regulation of the fibrinolytic system of cultured human vascular endothelium by interleukin 1. J Clin Invest 1986; 78: 587-591
38
De Groot PG,
Verweij CL,
Nawroth PP,
de Boer HC,
Stem DM,
Sixma JJ.
Interleukin-1 inhibits the synthesis of von Willebrand factor in endothelial cells, which results in a decreased reactivity of their matrix toward platelets. Arteriosclerosis 1987; 7: 605-611
39
Giddings JC,
Shall L.
Enhanced release of von Willebrand factor by human endothelial cells in culture in the presence of phorbol myristate acetate and interleukin 1. Thromb Res 1987; 47: 259-267
40
Schorer AE,
Moldow CF,
Rick ME.
Interleukin 1 or endotoxin increases the release of von Willebrand factor from human endothelial cells. Br J Haematol 1987; 67: 193-197
