[en] 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.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Li, X. R.
Tjwa, M.
Moons, L.
Fons, P.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Ny, A.
Zhou, J. M.
Lennartsson, J.
Li, H.
Luttun, A.
Ponten, A.
Devy, L.
Bouche, A.
Oh, H.
Manderveld, A.
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Communi, D.
Savi, P.
Bono, F.
Dewerchin, M.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Li, X., et al. 2000. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat. Cell Biol. 2:302-309.
Bergsten, E., et al. 2001. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat. Cell Biol. 3:512-516.
LaRochelle, W.J., et al. 2001. PDGF-D, a new protease-activated growth factor. Nat. Cell Biol. 3:517-521.
Heldin, C.H., and Wescermark, B. 1999. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 79:1283-1316.
Gilbertson, D.G., et al. 2001. Platelet-derived growth factor C (PDGF-C) a novel growth factor that binds to PDGF alpha and beta receptor. J. Biol. Chem. 276:27406-27414.
Resink, T.J., et al. 1990. Specific growth stimulation of cultured smooth muscle cells from spontaneously hypertensive rats by platelet-derived growth factor A-chain homodimer. Cell Regul. 1:821-831.
Hellstrom, M., Kalen, M., Lindahl, P., Abramsson, A., and Betsholtz, C. 1999. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 126:3047-3055.
Hellstrom, M., et al. 2001. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol. 153:543-553.
Hirschi, K.K., Rohovsky, S.A., Beck, L.H., Smith, S.R., and D'Amore, P.A. 1999. Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ. Res. 84:298-305.
Lindahl, P., and Betsholtz, C. 1998. Not all myofibroblasts are alike: revisiting the role of PDGF-A and PDGF-B using PDGF-targeted mice. Curr. Opin. Nephrol. Hypertens. 7:21-26.
Hoch, R.V., and Soriano, P. 2003. Roles of PDGF in animal development. Development. 130:4769-4784.
Guo, P., et al. 2003. Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment. Am. J. Pathol. 162:1083-1093.
Furuhashi, M., et al. 2004. Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate. Cancer Res. 64:2725-2733.
Sato, N., et al. 1993. Platelet-derived growth factor indirectly stimulates angiogenesis in vitro. Am. J. Pathol. 142:1119-1130.
Benjamin, L.E., Hemo, I., and Keshet, E. 1998. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development. 125:1591-1598.
Richardson, T.P., Peters, M.C., Ennett, A.B., and Mooney, D.J. 2001. Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19:1029-1034.
Hao, X., et al. 2004. Angiogenic effects of dual gene transfer of bFGF and PDGF-BB after myocardial infarction. Biochem. Biophys. Res. Commun. 315:1058-1063.
Cao, R., et al. 2003. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat. Med. 9:604-613.
Pietras, K., et al. 2002. Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res. 62:5476-5484.
Erber, R., et al. 2004. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 18:338-340.
Uehara, H., et al. 2003. Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. J. Natl. Cancer Inst. 95:458-470.
Kim, S.J., et al. 2004. Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice. Cancer Res. 64:4201-4208.
Wilkinson-Berka, J.L., et al. 2004. Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy. Am. J. Pathol. 164:1263-1273.
Koyama, N., et al. 1994. Migratory and proliferative effect of platelet-derived growth factor in rabbit retinal endothelial cells: evidence of an autocrine pathway of platelet-derived growth factor. J. Cell. Physiol. 158:1-6.
Marx, M., Perlmutter, R.A., and Madri, J.A. 1994. Modulation of platelet-derived growth factor receptor expression in microvascular endothelial cells during in vitro angiogenesis. J. Clin. Invest. 93:131-139.
Smits, A., et al. 1989. Rat brain capillary endothelial cells express functional PDGF B-type receptors. Growth Factors. 2:1-8.
Battegay, E.J., Rupp, J., Iruela Arispe, L., Sage, E.H., and Pech, M. 1994. PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF beta-receptors. J. Cell Biol. 125:917-928.
Thommen, R., et al. 1997. PDGF-BB increases endothelial migration on cord movements during angiogenesis in vitro. J. Cell. Biochem. 64:403-413.
Beitz, J.G., Kim, I.S., Calabresi, P., and Frackelcon, A.R., Jr. 1991. Human microvascular endothelial cells express receptors for platelet-derived growth factor. Proc. Natl. Acad. Sci. U. S. A. 88:2021-2025.
Plate, K.H., Breier, G., Farrell, C.L., and Risau, W. 1992. Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab. Invest. 67:529-534.
Bar, R.S., et al. 1989. The effects of platelet-derived growth factor in cultured microvessel endothelial cells. Endocrinology. 124:1841-1848.
Lindahl, P., et al. 1998. Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli. Development. 125:3313-3322.
Lindner, V., and Reidy, M.A. 1995. Platelet-derived growth factor ligand and receptor expression by large vessel endothelium in vivo. Am. J. Pathol. 146:1488-1497.
Edelberg, J.M., et al. 1998. PDGF mediates cardiac microvascular communication. J. Clin. Invest. 102:837-843.
Cao, R., et al. 2002. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-alphaalpha and -alphabeta receptors. FASEB J. 16:1575-1583.
Oikawa, T., Onozawa, C., Sakaguchi, M., Morita, I., and Murota, S. 1994. Three isoforms of platelet-derived growth factors all have the capability to induce angiogenesis in vivo. Biol. Pharm. Bull. 17:1686-1688.
Risau, W., et al. 1992. Platelet-derived growth factor is angiogenic in vivo. Growth Factors. 7:261-266.
De Marchis, F., et al. 2002. Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its alpha receptor. Blood. 99:2045-2053.
Uutela, M., et al. 2001. Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFD genes. Circulation. 103:2242-2247.
Li, H., Fredriksson, L., Li, X., and Eriksson, U. 2003. PDGF-D is a potent transforming and angiogenic growth factor. Oncogene. 22:1501-1510.
Luttun, A., et al. 2002. Revascularization of ischemic tissues by P1GF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat. Med. 8:831-840.
Palumbo, R., et al. 2002. Different effects of high and low shear stress on platelet-derived growth factor isoform release by endothelial cells: consequences for smooth muscle cell migration. Arterioscler. Thromb. Vasc. Biol. 22:405-411.
Rafii, S. 2000. Circulating endothelial precursors: mystery, reality, and promise. J. Clin. Invest. 105:17-19.
Miraglia, S., et al. 1997. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 90:5013-5021.
Ekman, S., Thuresson, E.R., Heldin, C.H., and Ronnstrand, L. 1999. Increased mitogenicity of an alphabeta heterodimeric PDGF receptor complex correlates with lack of RasGAP binding. Oncogene. 18:2481-2488.
Blacher, S., et al. 2001. Improved quantification of angiogenesis in the rat aortic ring assay. Angiogenesis. 4:133-142.
Poncen, A., et al. 2003. Transgenic overexpression of platelet-derived growth factor-C in the mouse heart induces cardiac fibrosis, hypertrophy, and dilated cardiomyopathy. Am. J. Pathol. 163:673-682.
Apte, S.M., Fan, D., Killion, J.J., and Fidler, I.J. 2004. Targeting the platelet-derived growth factor receptor in antivascular therapy for human ovarian carcinoma. Clin. Cancer Res. 10:897-908.
Betsholtz, C., Karlsson, L., and Lindahl, P. 2001. Developmental roles of platelet-derived growth factors. Bioessays. 23:494-507.
Ding, H., et al. 2004. A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling. Nat. Genet. 36:1111-1116.
Buschmann, I., Heil, M., Jost, M., and Schaper, W. 2003. Influence of inflammatory cytokines on arteriogenesis. Microcirculation. 10:371-379.
Hudkins, K.L., et al. 2004. Exogenous PDGF-D is a potent mesangial cell mitogen and causes a severe mesangial proliferative glomerulopathy. J. Am. Soc. Nephrol. 15:286-298.
Schaeren-Wiemers, N., and Gerfin-Moser, A. 1993. A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-label led cRNA probes. Histochemistry. 100:431-440.
Eriksson, A., Siegbahn, A., Westermark, B., Heldin, C.H., and Claesson-Welsh, L. 1992. PDGF alpha- and beta-receptors activate unique and common signal transduction pathways. EMBO J. 11:543-550.
Dimmeler, S., et al. 2001. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J. Clin. Invest. 108:391-397. doi:10.1172/JCI200113152.