Modulation by leptin of proliferation and apoptosis in vascular endothelial cells.
OBJECTIVE
Plasma leptin concentrations not only correlate with body fat mass, but also with the degree of hypertensive retinopathy. The present study was designed to further examine, whether leptin's proliferative, proangiogenic activity relates to a yet uncovered anti-apoptotic effect.


RESULTS
Leptin (10-50 nmol/l) concentration-dependently reduced apoptosis in HUVECs (human umbilical vein endothelial cells), HAVECs (human adult vein endothelial cells) and HMECs (human microvascular endothelial cells) by 20% (P < or = 0.05). These findings were supported by increased expression of the apoptosis inhibitor bcl-2 (+55%, P < or = 0.05) as well as by differential modulation of the respective cell cycle checkpoint genes/proteins p53 (-20%, P < or = 0.01), p21(WAF-1/Cip1) (-23%, P < or = 0.05) and the Retinoblastoma protein (+123%, P < or = 0.01).


CONCLUSIONS
bcl-2 dependent anti-apoptotic action might contribute to leptin's proangiogenic activity and thereby promote the development of vascular proliferative disease in obesity.
Artwohl
M
M
Department of Internal Medicine III, University of Vienna, Austria.
Roden
M
M
Hölzenbein
T
T
Freudenthaler
A
A
Waldhäusl
W
W
Baumgartner-Parzer
S M
SM
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008833:Microcirculation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000098:blood supply; D014471:Umbilical Veins; D014599:Uterus / Q000098:blood supply; D014680:Veins
D020738:Leptin; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger