Disruption of Platelet-Derived Growth Factor–Dependent Phosphatidylinositol 3-Kinase and Phospholipase Cγ 1 Activity Abolishes Vascular Smooth Muscle Cell Proliferation and Migration and Attenuates Neointima Formation In Vivo

Publication year: 2011
Source: Journal of the American College of Cardiology, Volume 57, Issue 25, 21 June 2011, Pages 2527-2538

Evren, Caglayan , Marius, Vantler , Olli, Leppänen , Felix, Gerhardt , Lenard, Mustafov , …

 Objectives: We tested the hypothesis whether selective blunting of platelet-derived growth factor (PDGF)–dependent vascular smooth muscle cell (VSMC) proliferation and migration is sufficient to prevent neointima formation after vascular injury. Background: To prevent neointima formation and stent thrombosis after coronary interventions, it is essential to inhibit VSMC proliferation and migration without harming endothelial cell function. The role of PDGF—a potent mitogen and chemoattractant for VSMC that does not affect endothelial cells—for neointima formation remains controversial. Methods: To decipher the signaling pathways that control PDGF beta receptor (βPDGFR)–driven VSMC proliferation and migration, we characterized 2 panels of chimeric CSF1R/βPDGFR mutants in which the binding sites for…