Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: Role of PDGF-β receptor and Src

Shu Q. Liu*, Christopher Tieche, Dalin Tang, Paul Alkema

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Blood vessels are subject to fluid shear stress, a hemodynamic factor that inhibits the mitogenic activities of vascular cells. The presence of nonuniform shear stress has been shown to exert graded suppression of cell proliferation and induces the formation of cell density gradients, which in turn regulate the direction of smooth muscle cell (SMC) migration and alignment. Here, we investigated the role of platelet-derived growth factor (PDGF)-β receptor and Src in the regulation of such processes. In experimental models with vascular polymer implants, SMCs migrated from the vessel media into the neointima of the implant under defined fluid shear stress. In a nonuniform shear model, blood shear stress suppressed the expression of PDGF-β receptor and the phosphorylation of Src in a shear level-dependent manner, resulting in the formation of mitogen gradients, which were consistent with the gradient of cell density as well as the alignment of SMCs. In contrast, uniform shear stress in a control model elicited an even influence on the activity of mitogenic molecules without modulating the uniformity of cell density and did not significantly influence the direction of SMC alignment. The suppression of the PDGF-β receptor tyrosine kinase and Src with pharmacological substances diminished the gradients of mitogens and cell density and reduced the influence of nonuniform shear stress on SMC alignment. These observations suggest that PDGF-β receptor and Src possibly serve as mediating factors in non-uniform shear-induced formation of cell density gradients and alignment of SMCs in the neointima of vascular polymer implants.

Original languageEnglish (US)
Pages (from-to)H1081-H1090
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number3 54-3
StatePublished - Sep 1 2003

Keywords

  • Cell alignment
  • Cell density gradients
  • Cell migration
  • Mitogen gradients
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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