Effects of Simvastatin on Reorganization of Focal Adhesion and Actin Cytoskeleton in Vascular Smooth Muscle Cells Induced by Platelet-Derived Growth Factor-BB

doi:10.3877/cma.j.issn.1673-5250.2008.05.104

Objective

To investigate the relationship between proliferation and migration of rats vascular smooth muscle cell(VSMC) and cytoskeleton in vascular smooth muscle cells by observation on effects of simvastatin on reorganization of focal adhesion (FA) and actin cytoskeleton in vascular smooth muscle cells induced by platelet-derived grwoth factor (PDGF-BB).

Methods

vascular smooth muscle cells isolated from pulmonary media of SD rats and cultured were adopted.Observation on proliferation and changes of phenotype of vascular smooth muscle cells by using [³H]thymidine uptake and electron microscopy.The dynamic assemble of focal adhesion and reorganization of the actin cytoskeleton of PDGF-BB-induced vascular smooth muscle cells were studied by immunocytochemistry and fluorocytochemistry techniques after treated with simvastatin.

Results

Treatment with PDGF-BB for 24 h resulted in a substantial increase in [³H]thymidine uptake and evident change in phenotype under electron microscopy.There were corresponding increase in the number and size of paxillin-positive focal adhesion and stress fibers and rearrangement of these structures into ordered parallel arrays.Simvastatin could inhibit significantly these biological effects.

Conclusion

Simvastatin could inhibit the dynamic assemble of focal adhesion and F-actin and α-SM-actin in PDGF-BB-induced vascular smooth muscle cells, and then inhibit proliferation and migration of vascular smooth muscle cells.

Key words: simvastatin, vascular smooth muscle cell, cytoskeleton

图1　在含10%FBS的M199培养液中单层生长的VSMC

图2　肺动脉VSMC的超微结构(×6000)

图3　VSMC内Paxillin阳性粘着斑表达(×400)

图4　VSMC内收缩表型蛋白α－SM－actin阳性表达(×400)

图5　VSMC内F－actin荧光染色

	1　Jeffery TK, Morrell NW. Molecular and celluar basis of vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis, 2002，45(3): 173－202.
	2　Eguchi S, Iwasaki H, Inagami T，et al. Involvement of PYK2 in angiotensin Ⅱ signaling of vascular smooth muscle cells. Hypertension, 1999, 33 (1 Pt 2): 201－206.
	3　Walter DH，Schachinger V，Elsner M，et al.Effect of statin therapy on restenosis after coronary stent implantation.Am J Cardiol，2000，85：962－968.
	4　Rowe VL, Stevens SL, Reddick TT, et al. Vascular smooth muscle cell apoptosis in aneurysmal, occlusive and normal human aortas. J Vasc Surg 2000，31(3): 567－576.
	5　Cary LA, Guan JL. Focal adhesion kinase in integrin－mediated signaling. Front Biosci, 1999, 4(3): D102－113.
	6　Castellano F, Montcourrier P, Guillemot JC，et al.Inducible recruitment of Cdc42 or WASP to a cell－surface receptor triggers actin polymerization and filopodium formation. Curr Biol, 1999, 9(7): 351－360.
	7　Kato T, Hashikabe H, Iwata C, et al. Statin blocks Rho/Rho－kinase signalling and disrupts the actin cytoskeleton: Relationship to enhancement of LPS－mediated nitric oxide synthesis in vascular smooth muscle cells. Biochem Biophys Acta，2004，1689(3): 267－272.

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