Split for the cure: VEGF, PDGF-BB and intussusception in therapeutic angiogenesis.
Therapeutic angiogenesis is an attractive strategy to treat patients suffering from ischaemic conditions and vascular endothelial growth factor-A (VEGF) is the master regulator of blood vessel growth. However, VEGF can induce either normal or aberrant angiogenesis depending on its dose localized in the microenvironment around each producing cell in vivo and on the balanced stimulation of platelet-derived growth factor-BB (PDGF-BB) signalling, responsible for pericyte recruitment. At the doses required to induce therapeutic benefit, VEGF causes new vascular growth essentially without sprouting, but rather through the alternative process of intussusception, or vascular splitting. In the present article, we briefly review the therapeutic implications of controlling VEGF dose on one hand and pericyte recruitment on the other, as well as the key features of intussusceptive angiogenesis and its regulation.
Roberto
R
Gianni-Barrera
*Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Mariateresa
M
Bartolomeo
†Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee, D-18057 Rostock, Germany.
Brigitte
B
Vollmar
‡Institute of Anatomy, University of Bern, Baltzerstrasse 2, CH-3000 Bern, Switzerland.
Valentin
V
Djonov
*Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Andrea
A
Banfi
D050197:Atherosclerosis / Q000188:drug therapy / Q000628:therapy*; D000077214:Becaplermin; D001775:Blood Circulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018919:Neovascularization, Physiologic; D020574:Proto-Oncogene Proteins c-sis / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin