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.
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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

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Effects of PDGF-CC on endothelial progenitors. (A) PDGF-CC treatment inc...
Effects of PDGF-CC on endothelial progenitors. (A) PDGF-CC treatment increased EPC mobilization from day 2 to day 5 after hind limb ischemia but did not affect EPC mobilization in normal conditions. *P < 0.05. Values are mean ± SEM of 10 mice. (B–D) Double labeling of EPCs for PDGF-Rα (green in B) and Dil-ac-LDL (red in C), showing coexpression (yellow in D). (E–P) After 2 weeks of stimulation, both PDGF-CC and VEGF induced the expression of EC surface markers CD144 (VE-cadherin) and CD31 (PECAM), while vehicle-treated cells remained negative. Only PDGF-CC induced prominent α-SMA expression, while cells treated with VEGF or vehicle displayed background levels of α-SMA expression. Unstained cells in E–G show that both VEGF and PDGF-CC promoted stem/progenitor cell adherence.