PDGF MEDIATES CARDIAC MICROVASCULAR COMMUNICATION

The diversity of cellular and tissue functions within organs requires that local communication circuits control distinct populations of cell s. Recently, we reported that cardiac myocytes regulate the expression of both von Willebrand factor (vWF) and a transgene with elements of the vWF promoter in a subpopulation of cardiac microvascular endotheli al cells (J. Cell Biol, 138:1117). The present study explores this com munication. Histological examination of the cardiac microvasculature r evealed colocalization of the vWF transgene with the PDGF cr-receptor. Transcript analysis demonstrated that in vitro cardiac microvascular endothelial cells constitutively express PDGF-A, but not B. Cardiac my ocytes induced endothelial expression of PDGF-B, resulting in PDGF-AB, Protein measurement and transcript analysis revealed that PDGF-AB, bu t not PDGF-AA, induced endothelial expression of vWF and its transgene . Antibody neutralization of PDGF-AB blocked the myocyte-mediated indu ction. Immunostaining demonstrated that vWF induction is confined to P DGF a-receptor-positive endothelial cells. Similar experiments reveale d that the PDGF-AB/alpha-receptor communication also induces expressio n of vascular endothelial growth factor and Flk-1, critical components of angiogenesis. The existence of this communication pathway was conf irmed in vivo. Injection of PDGF-AB neutralizing antibody into the amn iotic fluid surrounding murine embryos extinguished expression of the transgene, In summary, these studies suggest that environmental induct ion of PDGF-AB/alpha-receptor interaction is central to the regulation of cardiac microvascular endothelial cell hemostatic and angiogenic a ctivity.