In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 301, No. 5 ( 2011-11), p. H1781-H1787
Kurzfassung:
This study examines the effects of VEGF-121 therapy in an animal model of preeclampsia induced by overexpression of soluble VEGF receptor 1 (sVEGFR-1). At day 8 of gestation, CD-1 mice were implanted with subcutaneous osmotic pumps containing either VEGF-121 or vehicle and fitted with telemetric blood pressure (BP) catheters for continuous BP monitoring ( days 8–18 of gestation). On day 9, the animals in the VEGF-121 group were randomly allocated for injection with adenovirus carrying sVEGFR-1 or the murine immunoglobulin G2α Fc fragment (mFc) as virus control (Adv-sVEGFR-1; Adv-mFc). Animals in the vehicle group were injected with Adv-sVEGFR-1. On day 18, mice were euthanized, placentas and pups weighted, carotid arteries isolated, and their responses studied in vitro using a wire myograph for isometric tension recording. In mice overexpressing sVEGFR-1, treatment with VEGF-121 significantly reduced BP from days 10 to 18 of gestation compared with that of vehicle. VEGF-sVEGFR-1 animals had significantly higher vasorelaxant response to sodium nitroprusside and significantly lower contractile response to the thromboxane agonist (U-46619) compared with that of the vehicle-sVEGFR-1 mice. Phenylephrine and acetylcholine responses did not significantly vary between the VEGF-sVEGFR-1 and the vehicle-sVEGFR-1 mice. Average pup weight was significantly lower in the vehicle-sVEGFR-1 group compared with the VEGF-sVEGFR-1 and VEGF-mFc groups. In conclusion, VEGF-121 therapy attenuates vascular dysfunction and diminishes intrauterine growth abnormality in an animal model of preeclampsia induced by overexpression of sVEGFR-1. Modulation of VEGF pathway turns into a promising therapeutic approach of preeclampsia.
Materialart:
Online-Ressource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00373.2011
Sprache:
Englisch
Verlag:
American Physiological Society
Publikationsdatum:
2011
ZDB Id:
1477308-9
SSG:
12
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