Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors
Xuri Li, … , Ulf Eriksson, Peter Carmeliet
Xuri Li, … , Ulf Eriksson, Peter Carmeliet
Published January 3, 2005
Citation Information: J Clin Invest. 2005;115(1):118-127. https://doi.org/10.1172/JCI19189.
View: Text | PDF
Article Cardiology

Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors

Abstract

The angiogenic mechanism and therapeutic potential of PDGF-CC, a recently discovered member of the VEGF/PDGF superfamily, remain incompletely characterized. Here we report that PDGF-CC mobilized endothelial progenitor cells in ischemic conditions; induced differentiation of bone marrow cells into ECs; and stimulated migration of ECs. Furthermore, PDGF-CC induced the differentiation of bone marrow cells into smooth muscle cells and stimulated their growth during vessel sprouting. Moreover, delivery of PDGF-CC enhanced postischemic revascularization of the heart and limb. Modulating the activity of PDGF-CC may provide novel opportunities for treating ischemic diseases.

Authors

Xuri Li, Marc Tjwa, Lieve Moons, Pierre Fons, Agnes Noel, Annelii Ny, Jian Min Zhou, Johan Lennartsson, Hong Li, Aernout Luttun, Annica Pontén, Laetitia Devy, Ann Bouché, Hideyasu Oh, Ann Manderveld, Silvia Blacher, David Communi, Pierre Savi, Françoise Bono, Mieke Dewerchin, Jean-Michel Foidart, Monica Autiero, Jean-Marc Herbert, Désiré Collen, Carl-Henrik Heldin, Ulf Eriksson, Peter Carmeliet

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Tyrosine phosphorylation of PDGF-Rα and downstream proteins in response ...
Tyrosine phosphorylation of PDGF-Rα and downstream proteins in response to PDGF-CC. (A) Immunoprecipitation of equal amounts of PAEC/Rα extracts for PDGF-Rα and subsequent immunoblotting for pTyr, revealing a higher degree of PDGF-Rα tyrosine phosphorylation after 10-minute stimulation with PDGF-BB or -CC than with PDGF-AA. The lower panel shows an immunoblot of PDGF-Rα, displaying the amount of receptor present in each sample. (B) Immunoblotting of equal amounts of PAEC/Rα extracts for pTyr after stimulation with PDGF-AA, -BB, or -CC for 10 minutes, revealing that a similar set of proteins (judged on the basis of their molecular weight) was phosphorylated but that, in general, the phosphorylation signals were stronger in response to PDGF-BB and -CC than PDGF-AA. The lower panel shows an immunoblot of PDGF-Rα, displaying the amount of receptor present in each sample. For both A and B, though equal amounts of cell lysate were immunoprecipitated (A) and/or loaded (A and B), PDGF-Rα levels differed among the various lanes, presumably reflecting effects on receptor internalization and degradation. PDGF-Rα is present as a doublet due to differences in glycosylation.