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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Figure 1

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Therapeutic revascularization with PDGF-CC in ischemic heart. (A–C) Immu...
Therapeutic revascularization with PDGF-CC in ischemic heart. (A–C) Immunostaining, revealing low PDGF-Rα expression in a subset of microvessels in an uninjured myocardium (A) and strongly increased PDGF-Rα expression in sprouting vessels in the border region of a myocardial infarct, from where vessels revascularize the infarct (B and C). C shows a detail of PDGF-Rα expression in microvessels (arrows). (D) Upper and middle panels: immunoprecipitation and subsequent Western blotting for PDGF-Rα (upper) and pTyr (middle) showed that PDGF-Rα was upregulated in the ischemic myocardial regions bordering the infarct where vessels start to grow. Note also that PDGF-Rα was activated more in the borders than the normal (nonischemic) regions and maximally after PDGF-CC treatment. Lower panel: Coomassie staining revealing comparable loading. (E and F) PDGF-CC protein treatment increased TM+ (E) and SMA+ (F) vessel density in the infarcted areas in a dose-dependent manner. *P < 0.05 vs. vehicle. (G–I) TM immunostaining of myocardial vessels, revealing increased vessel densities after PDGF-CC treatment. (J–L) α-SMA immunostaining of myocardial vessels, revealing increased vessel densities after PDGF-CC treatment. Scale bars: 50 μm in A, B, G–L and 20 μm in C.