Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery.

Abstract

Intimal Platelets are thought to play a major role in the formation of arterial intimal lesions (1, 2) by releasing, at sites of endothelial denudation, growth factors that stimulate smooth muscle cell (SMC) growth. Support for the role of platelets in vivo comes from the key study of Friedman et al. (3), in which these authors showed that experimentally induced intimal lesion formation in rabbit arteries was significantly inhibited by prolonged thrombocytopenia. This study was interpreted by others to suggest that platelets play an important role in the induction of SMC replication, even though no cell cycle data were presented. An alternative hypothesis is that platelets and their mitogens were important in initiating migration of cells into the intima. In this regard, platelet-derived growth factor (PDGF) has been shown to be chemotactic for mesenchymal cells (4,5). The goal of this study was to determine whether, after balloon catheter denudation, inhibition of platelet adherence influenced SMCs in terms of early mRNA expression and cell proliferation. To accomplish this, we used a single injection of a polyclonal antibody against rat platelets that prevented their adherence to the subendothelium for more than 24 hr after injury. Using this protocol, we were able to show that the absence of platelets did not affect the early proliferation of SMCs in response to injury but did inhibit formation of intimal lesions. We conclude that after balloon catheter injury platelets play a minor role in promoting medial proliferation but are important in the stimulation of SMC migration into the intima.

Altered Vascular Injury Responses in Mice Deficient in Protease-Activated Receptor-1

“…32,33 The response to thrombin in mouse and rat platelets appears to be mediated by PAR-3 and PAR-4, 42,43 2 distinct protease-activated thrombin receptors. Because platelet adhesion, aggregation, and degranulation are important components of the vascular injury process, 44,45 these plateletdependent processes would not be affected in PAR-1-deficient mice. Therefore, our mouse model does not assess the contribution of thrombin-induced platelet aggregation to the vascular injury response.…”

Activation of Mitogen-activated Protein Kinase Pathways by Cyclic GMP and Cyclic GMP-dependent Protein Kinase in Contractile Vascular Smooth Muscle Cells

“…Vascular smooth muscle cell (VSMC) 1 proliferation and migration are associated with several vascular diseases such as atherosclerosis and restenosis following vascular injury (1)(2)(3)(4)(5). VSMC from several species when cultured in vitro undergo a change in phenotype from a contractile state to a synthetic state similar to the changes that occur with VSMC in vivo in response to vascular injury (6 -8).…”

Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury.

“…We have previously shown that platelet depletion inhibits intimal thickening in balloon-injured rat arteries but does not affect SMC replication, suggesting that platelets stimulate migration. 4 Data are now beginning to emerge that suggest that platelet-derived growth factor (PDGF) may be an important mediator of migration. Administration of exogenous PDGF to rats causes a marked stimulation of intimal SMC accumulation 5 but has little effect on the replication rate of these cells.…”