Mechanistic and therapeutic implications of angiogenesis in endometriosis.
Like tumor metastases, endometriotic implants require neovascularization to proliferate and invade into ectopic sites within the host. Endometrial tissue, with its robust stem cell populations and remarkable regenerative capabilities, is a rich source of proangiogenic factors. Among the most potent and extensively studied of these proteins, vascular endothelial growth factor has emerged as a critical vasculogenic regulator in endometriosis. Accordingly, angiogenesis of the nascent endometriotic lesion has become an attractive target for novel medical therapeutics and strategies to inhibit vascular endothelial growth factor action. Vascular endothelial growth factor gene regulation in endometrial and endometriosis cells by nuclear receptors, other transcription factors, and also by infiltrating immune cells is emphasized. New data showing that oxidative and endoplasmic reticulum stress increase vascular endothelial growth factor expression are provided. Finally, we review the clinical implications of angiogenesis in this condition and propose potential antiangiogenic therapies that may become useful in the control or eradication of endometriotic lesions.
Taylor
Robert N
RN
Department of Gynecology and Obstetrics, Human Uterine Biology Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA. robert.n.taylor@emory.edu
Yu
Jie
J
Torres
Paulo B
PB
Schickedanz
Aimee C
AC
Park
John K
JK
Mueller
Michael D
MD
Sidell
Neil
N
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004717:Endometrium / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D018384:Oxidative Stress; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A