Effect of Heparin-Derived Oligosaccharide on Vascular Smooth Muscle Cell Proliferation

Abstract

In this study, the effect of heparin-derived oligosaccharide on bovine vascular smooth muscle cell (VSMC) proliferation and signal transduction mechanism was investigated. Extracellular-signal-regulated kinase (ERK) 1/2 has been implicated in the regulation of various cellular functions including proliferation, and we sought to define a functional role for ERK 1/2 in an established proliferation model in order to find a possible mechanism for inhibition of VSMC proliferation by heparin-derived oligosaccharide. The VSMC proliferation model was developed by platelet-derived growth factor (PDGF), and the level of ERK 1/2 protein and messenger RNA was determined by reverse transcriptase–polymerase chain reaction, Western blotting, and immunocytochemical methods. Flow cytometry analysis indicated that heparin-derived oligosaccharide blocked PDGF-induced cell cycle progression by arresting cells in the G0/G1 phase. The results imply that heparin-derived oligosaccharide inhibits VSMC proliferation by moderating the gene and the phosphorylation levels of ERK 1/2, eventually blocking G1/S transition, may be one of the mechanisms for inhibition of VSMC proliferation by heparin-derived oligosaccharide.

Keywords

heparin-derived oligosaccharide proliferation vascular smooth muscle cell (VSMC)ERK1/2

Get full access to this article

View all access options for this article.

References

Rivard

Andres

. Vascular smooth muscle cell proliferation in the pathogenesis of atherosclerotic cardiovascular diseases. Histol Histopathol. 2000;15(2):557–571.

Kastan

Bartek

. Cell-cycle checkpoints and cancer. Nature. 2004;432(7015):316–323.

Hommes

Peppelenbosch

van Deventer

. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 2003;52(1):144–151.

Leszczynski

Joenvaara

Foegh

. Protein kinase C-alpha regulates proliferation but not apoptosis in rat coronary vascular smooth muscle cells. Life Sci. 1996;58(7):599–606.

Kim

Yun

. Antiproliferative activity of NQ304, a synthetic 1, 4-naphthoquinone, is mediated via the suppressions of the PI3K/Akt and ERK1/2 signaling pathways in PDGF-BB-stimulated vascular smooth muscle cells. Vascul Pharmacol. 2007;46(1):43–51.

Wang

Qian

Zhou

Zhao

. JAK-STAT signaling pathway in pulmonary arterial smooth muscle cells is activated by hypoxia. Cell Biol Int. 2005;29(7):598–603.

Niu

Wang

. Preparation of heparin derived oligosaccharides and affection of them on vascular smooth muscle cells proliferation. Pharm Biotechnol. 2009;16(1):46–49.

Ross

. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362(6423):801–809.

Clowes

Schwartz

. Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res. 1985;56(1):139–145.

10.

Clowes

Reidy

Clowes

. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49(2):208–215.

11.

Ross

. Cell biology of atherosclerosis. Annu Rev Physiol. 1995;57:791–804.

12.

Faries

Rohan

Wyers

. Vascular smooth muscle cells derived from atherosclerotic human arteries exhibit greater adhesion, migration, and proliferation than venous cells. J Surg Res. 2002;104(1): 22–28.

13.

Chun

Qian

Bin

. Clinical effects of combination therapy with sodium ozagrel and low molecular weight heparin on progressive cerebral infarction. Chin J Clin Pharmacol Ther. 2008;13(3):336–338.

14.

Gao

Rahamthulla

Hang

John

Shuennwen

Charles

. Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via up-regulating CD44 expression. J Vasc Surg. 2011;5(53): 359–1367.

15.

Kastan

Bartek

. Cell-cycle checkpoints and cancer. Nature. 2004;432(7015):316–323.

16.

Chan

Fang

Lin

Yang

Hung

. Lycopene inhibits PDGF-BB-induced retinal pigment epithelial cell migration by suppression of PI3K/Akt and MAPK pathways. Biochem Biophys Res Commun. 2009;388(1):172–176.

17.

Lovicu

McAvoy

. FGF-induced lens cell proliferation and differentiation is dependent on MAPK (ERK1/2) signaling. Development. 2001;128(24):5075–5084.

18.

Hambruch

Haeqer

Dilly

Pfarrer

. EGF stimulates proliferation in the bovine placental trophoblast cell line F3 via Ras and MAPK. Placenta. 2010;31(1):67–74.

19.

Tsiani

Lekas

Fantus

Dlugosz

Whiteside

High glucose-enhanced activation of mesangial cell p38 MAPK by ET-1, ANG II, and platelet-derived growth factor. Am J Physiol Endocrinol Metab. 2002;282(1):161–169.

20.

Hommes

Peppelenbosch

van Deventer

. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 2003;52(1):144–151.

21.

Godeny

Sayeski

. ANG II-induced cell proliferation is dually mediated by c-Src/Yes/Fyn-regulated ERK1/2 activation in the cytoplasm and PKC zeta-controlled ERK1/2 activity within the nucleus. Am J Physiol Cell Physiol. 2006;291(6):1297–1307.

22.

Godeny

Sayeski

. ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1. Am J Physiol Cell Physiol. 2006;291(6):1308–1317.

23.

Hou

Yang

Zhao

Yuan

. Ferulic acid inhibits endothelial cell proliferation through NO down-regulating ERK1/2 pathway. J Cell Biochem. 2004;93(6):1203–1209.

24.

Zhao

. Preparation of carboxymethyl sulfoehitosans with differentially substituted regions. J Ocean Univ Qingdao. 2003;2(l):69–74.

25.

Lambreeht

Boilly

Le Bourhis

. Regulation of cell proliferation and urokinase plasminogen activation of human breast epithelial cells. Int Joncol. 1998;12(6):1397–1401.

26.

Hoffmann

. Carrageenans inhibit growth-faetoe binding. Biochem J. 1993;289(pt 2):289–331.

27.

Ustaeh

Him

. Platelet-derived growth factor signaling and human cancer. J Biochem Mol Biol. 2003;36(l):49–59.

28.

Takeuchi

Kanzawa

Kondo

. Inhibition of platelet-derived growth factors singalling induces autophagy in malignant glima cells. British J Cancer. 2004;90(5):1069–1075.

29.

Mentlein

Held-Feindt

. Angiogenesis factors in gliomas: a new key to tumor therapy? Naturwissenchaften. 2003;90(9):385–394.