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Titolo:
Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: Survival effect of vascular endothelial growth factor on circulating and unanchored endothelial cells
Autore:
Solovey, A; Gui, LZ; Ramakrishnan, S; Steinberg, MH; Hebbel, RP;
Indirizzi:
Univ Minnesota, Dept Med, Minneapolis, MN USA Univ Minnesota Minneapolis MN USA nnesota, Dept Med, Minneapolis, MN USA Univ Minnesota, Dept Pharmacol, Minneapolis, MN USA Univ Minnesota Minneapolis MN USA a, Dept Pharmacol, Minneapolis, MN USA Vet Affairs Med Ctr, Dept Med, Jackson, MS USA Vet Affairs Med Ctr Jackson MS USA rs Med Ctr, Dept Med, Jackson, MS USA
Titolo Testata:
BLOOD
fascicolo: 11, volume: 93, anno: 1999,
pagine: 3824 - 3830
SICI:
0006-4971(19990601)93:11<3824:SCAAAP>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; FACTOR RECEPTOR KDR; DIABETIC-RETINOPATHY; ANGIOGENESIS; DEATH; EXPRESSION; HYPOXIA; DISEASE; STIMULATION; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Hebbel, RP Box 480 UMHC,Harvard St & E River Rd, Minneapolis, MN 55455 USA Box 480 UMHC,Harvard St & E River Rd Minneapolis MN USA 55455
Citazione:
A. Solovey et al., "Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: Survival effect of vascular endothelial growth factor on circulating and unanchored endothelial cells", BLOOD, 93(11), 1999, pp. 3824-3830

Abstract

The biologic processes of apoptosis and angiogenesis are linked in endothelial biology because some endothelial cell growth factors also exert anti-apoptotic effects. We studied whether apoptosis is occurring in circulating endothelial cells (CEC) that have lost the survival signals derived from anchorage to extracellular matrix. Consistent with this expectation, 64% +/- 16% of CEC from normal donors showed evidence of apoptosis (by morphology and TdT-mediated dUTP nick end labeling [TUNEL] assay). However, only 30% +/- 15% (P < .001 v normal) of CEC from donors with sickle cell anemia were apoptotic. Vascular endothelial growth factor (VEGF) levels were significantly (P = .001) higher in plasma of sickle donors (120.1 +/- 81.4 pg/mL) thanthat of normal donors (37.6 +/- 34.6 pg/mL), and there was an inverse correlation between VEGF and CEC apoptosis (r = .612, P = .001). Consistent with stimulation by VEGF, CEC from sickle donors exhibited increased expression of alpha(v)beta(3). In vitro experiments showed that VEGF inhibits apoptosis for cultured endothelial cells that are kept unanchored and not allowedto re-establish attachment to extracellular matrix, thus demonstrating that VEGF provides survival signals independent of its ability to promote matrix reattachment. These data suggest the hypothesis that sickle cell anemia is a state of enhanced anti-apoptotic tone for endothelial cells. If true, this has im plications for disease pathobiology, particularly the development of neovascularizing retinopathy. (C) 1999 by The American Society of Hematology.

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Documento generato il 04/07/20 alle ore 11:14:42