Abstract 647: Identification of Platelet Derived Growth Factors A, B, C and D Specific Role in Vascular Remodeling

Abstract

Restenosis is a major complication after coronary angioplasty and stenting. The major cause of restenosis is neointimal hyperplasia, which results from an excessive proliferative response of vascular smooth muscle cells (VSMC) to mechanical injury. Platelet derived growth factor (PDGF) family members (A, B, C, D) are known to be related to vascular remodeling. However whether this role is specific for each one or overlapping remains to be elucidated. Aim: To assess the specific role of PDGF family members (A, B, C, D) in vascular remodeling after injury. Methods: We used an established model of balloon injury in rat carotid artery. The endothelium of the intima is mechanically removed. The animals (n=10/group) were sacrificed at different time points after injury (0-2-20 hours, 2-5-15 days, 6-12 weeks). mRNA from carotid arteries were isolated for gene expression studies using microarray gene expression. Results: PDGFs are differentially expressed in vascular remodeling (mRNA, A adj P val=3.28E-06, B adj P val=4.52E-8, C adj P val=5,91E-15, D adj P val=2,64E-18). Also the expression profile differs among them. We selected the genes highly correlated with each of the PDGFs (Spearman correlation, │rs >0.7│) and identified the most preeminent biological pathways associated to each one. PDGF-A positively correlates with program cell death. On the other hand, PDGF-B and C have some overlapping biological processes. There is positive correlation with blood vessel morphogenesis and angiogenesis (B), cell differentiation (B and C), DNA replication (B and C), antigen presentation and T-cell activation/differentiation (B and C). However, there is negative correlation with platelet activation (B) and cell adhesion (B and C). PDGF-D positively correlates with blood vessel morphogenesis and angiogenesis (like B) and cell differentiation (B, C), but is negatively correlated with T-cell activation/proliferation (opposite effect to B and C), apoptosis (opposite effect to A) and platelet activation (B). Conclusion: We identified specific biological processes for PDGF- A, B, C and D. Despite some overlapping, each one plays a specific role within vascular remodeling.