PDGF mediates cardiac microvascular communication.
The diversity of cellular and tissue functions within organs requires that local communication circuits control distinct populations of cells. 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 endothelial cells (J. Cell Biol. 138:1117). The present study explores this communication. Histological examination of the cardiac microvasculature revealed colocalization of the vWF transgene with the PDGF alpha-receptor. Transcript analysis demonstrated that in vitro cardiac microvascular endothelial cells constitutively express PDGF-A, but not B. Cardiac myocytes induced endothelial expression of PDGF-B, resulting in PDGF-AB. Protein measurement and transcript analysis revealed that PDGF-AB, but not PDGF-AA, induced endothelial expression of vWF and its transgene. Antibody neutralization of PDGF-AB blocked the myocyte-mediated induction. Immunostaining demonstrated that vWF induction is confined to PDGF alpha-receptor-positive endothelial cells. Similar experiments revealed that the PDGF-AB/alpha-receptor communication also induces expression of vascular endothelial growth factor and Flk-1, critical components of angiogenesis. The existence of this communication pathway was confirmed in vivo. Injection of PDGF-AB neutralizing antibody into the amniotic fluid surrounding murine embryos extinguished expression of the transgene. In summary, these studies suggest that environmental induction of PDGF-AB/alpha-receptor interaction is central to the regulation of cardiac microvascular endothelial cell hemostatic and angiogenic activity.
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
J M
JM
Edelberg
W C
WC
Aird
W
W
Wu
H
H
Rayburn
W S
WS
Mamuya
M
M
Mercola
R D
RD
Rosenberg
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000096:biosynthesis / Q000235:genetics
D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C095477:platelet-derived growth factor AB; D014841:von Willebrand Factor; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor