Summary
To investigate the role endothelial cells have on underlying smooth muscle cell proliferation, human aortic vascular smooth muscle cells were co-cultured with human aortic endothelial cells at different cell densities, using a transmembrane co-culture method. Subconfluent endothelial cells subseeded at low (0.5 × 104 cells/well) and medium densities (2.0 × 104 cells/well) stimulated smooth muscle cell proliferation by 43 ± 14% (P < 0.01) and 39 ± 8% (P < 0.02), respectively. However, this stimulatory effect on smooth muscle cell proliferation was not evident in confluent endothelial cells subseeded at high cell density (8.0 × 104 cells/well). Treatment of smooth muscle cells with trapidil, at 10−6M, for anti-platelet derived growth factor (PDGF) effect or with endothelin-1 receptor blocker FR 139317, at 10−6M failed to inhibit this stimulatory effect. These results imply that subconfluent human endothelial cells are able to exert a stimulatory effect on human smooth muscle cell proliferation, and that this endothelial paracrine growth effect may not be mediated by endothelin or PDGF.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Vanhoutte PM (1989) Endothelium and control of vascular function: State of the art lecture. Hypertension 13:658–667
Thomae KR, Nakayama DK, Billiar TR, Simmons RL, Pitt BR, Davies P (1995) The effect of nitric oxide on fetal pulmonary artery smooth muscle growth. J Surg Res 59:337–343
Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic GMP inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83:1774–1777
Akopov SE, Orekhov AN, Tertov VV, Khashimov KA, Gabrielyan ES, Smirinov VN (1988) Stable analogues of prostacyclin and thromboxane A display contradictory influences on atherosclerotic properties of cells cultured from human aorta: The effect of calcium antagonists. Atherosclerosis 72:245–248
Nakai T, Ohta M, Kato R (1991) Inhibition by prostacyclin and carbacyclins of endothelin-induced DNA synthesis in cultured vascular smooth muscle cells. Prostag Leukotr Ess 44:237–239
Komuro I, Kurihara H, Sugiyama T, Takaku F, Yazaki Y (1988) Endothelin stimulates c-fos and c-myc expression and proliferaton of vascular smooth muscle cells. FEBS Lett 238:249–459
Janakidevi K, Fisher MA, Del-Vecchio PJ, Tiurppathi C, Figge J, Malik AB (1992) Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells. Am J Physiol 263:C1295-C1301
Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s (1992) Nature 362:801–809
Sogabe K, Nirei H, Shoubo M, Nomoto A, Ao S, Notsu Y, Ono T (1993) Pharmacological profile of FR 139317, a novel, potent endothelin ET-A receptor antagonist. J Pharmacol Exp Ther 264:1040–1046
Ohinshi H, Yamaguchi K, Shimada S, Suzuki Y, Kumagai A (1981) A new approach to the treatment of atherosclerosis and trapidil as an antagonist to platelet-derived growth factor. Life Sci 28:1641–1646
Kuratsu J, Ushio Y (1990) Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitro. J Neurosurg 73:436–440
Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantites fo protein utilizing the principle of protein-dye binding. Ann Biochem 72:248–254
Gadjusek CM, DiCorleto P, Ross R, Schwartz S (1980) An endothelial cell-derived growth factor. J Cell Biol 85:467–472
Graham JD, Alexander JJ, Miguel R (1991) Aortic endothelial and smooth muscle cell co-culture: An in vitro model of the arterial wall. J Invest Surg 4:487–494
Axel D, Roth D, Betz E (1992) A transfilter culture system with human vascular cells. An in vitro model for the inner parts of a vessel wall? Eur Heart J 13 (Suppl):28
Xu CB, Pessah-Rasmussen H, Stavenow L (1991) Interactions between cultured bovine arterial endothelial and smooth muscle cells: Effects of injury on the release of growth stimulating and growth inhibiting substances. Pharmacol Toxicol 69:195–200
Takagi Y, Fukase M, Takata S, Yoshimi H, Takunaga O, Fujita T (1990) Autocrine effect of endothelin on DNA synthesis in human vascular endothelial cells. Biochem Biophys Res Commun 168:537–543
Saijonmaa O, Nyman T, Fyhrquist F (1992) Endothelin-1 stimulates its own synthesis in human endothelial cells. Biochem Biophys Res Commun 188:286–291
Peiro C, Redondo J, Rodriguz-Martinez MA, Angulo J, Sanchez-Ferrer CF (1995) Influence of endothelium on cultured vascular smooth muscle cell proliferation. Hypertension 25:748–751
Yoshida H, Nakamura M, Makita S, Hiramori K (1994) Inhibitory effect of atrial natruretic peptide on accelerated endothelin secretion from cultured human endothelial cells. J Atheroscler Thromb 1:76–79
Michiels C, De-Leener F, Arnorld T, Dieu M, Remacle J (1994) Hypoxia stimulates human endothelial cells to release smooth muscle cell mitogens: Role of prostaglandins and bFGF. Exp Cell Res 213:43–54
Scott-Burden T, Vanhoutte PM (1993) The endothelium as a regulator of vascular smooth muscle proliferation. Circulation 87:v51-v55
Furuya M, Yoshida M, Hayashi Y, Ohnuma N, Minamino N, Kangawa K, Matsuo H (1991) C-type natriuretic peptide is a growth inhibitor of rat vascular smooth muscle cells. Biochem Biophys Res Commun 177:927–931
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yoshida, H., Nakamura, M., Makita, S. et al. Paracrine effect of human vascular endothelial cells on human vascular smooth muscle cell proliferation: Transmembrane co-culture method. Heart Vessels 11, 229–233 (1996). https://doi.org/10.1007/BF01746202
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01746202