Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of FGF-2.
Pulsed electromagnetic fields (PEMF) have been shown to be clinically beneficial, but their mechanism of action remains unclear. The present study examined the impact of PEMF on angiogenesis, a process critical for successful healing of various tissues. PEMF increased the degree of endothelial cell tubulization (sevenfold) and proliferation (threefold) in vitro. Media from PEMF cultures had a similar stimulatory effect, but heat denaturation ablated this activity. In addition, conditioned media was able to induce proliferative and chemotactic changes in both human umbilical vein endothelial cells and fibroblasts, but had no effect on osteoblasts. Angiogenic protein screening demonstrated a fivefold increase in fibroblast growth factor beta-2 (FGF-2), as well as smaller increases in other angiogenic growth factors (angiopoietin-2, thrombopoietin, and epidermal growth factor). Northern blot analysis demonstrated an increase in FGF-2 transcription, and FGF-2 neutralizing antibody inhibited the effects of PEMF. In vivo, PEMF exposure increased angiogenesis more than twofold. We conclude that PEMF augments angiogenesis primarily by stimulating endothelial release of FGF-2, inducing paracrine and autocrine changes in the surrounding tissue. These findings suggest a potential role for PEMF in therapeutic angiogenesis.
Tepper
Oren M
OM
New York University Medical Center, Institute of Reconstructive Plastic Surgery, New York, New York 10016, USA .
Callaghan
Matthew J
MJ
Chang
Edward I
EI
Galiano
Robert D
RD
Bhatt
Kirit A
KA
Baharestani
Samuel
S
Gan
Jean
J
Simon
Bruce
B
Hopper
Richard A
RA
Levine
Jamie P
JP
Gurtner
Geoffrey C
GC
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D003094:Collagen; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004261:DNA Replication / Q000528:radiation effects; D004338:Drug Combinations; D004574:Electromagnetic Fields; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D007797:Laminin; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000528:radiation effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D019899:Paracrine Communication; D011453:Prostaglandins / Q000096:biosynthesis; D011509:Proteoglycans; D051381:Rats; D016037:Single-Blind Method; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D011453:Prostaglandins; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen