Angiogenesis in the primate ovary

2001 ◽  
Vol 13 (8) ◽  
pp. 557 ◽  
Author(s):  
Hamish M. Fraser ◽  
Christine Wulff
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Corpus Luteum ◽  
Expression Patterns ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Endothelial Cell Proliferation ◽  
Cell Proliferation Inhibition ◽  
Cyclic Changes

The ovary is distinctive in undergoing cyclic changes in angiogenesis that play a critical role in the normal functioning of the female reproductive system. The current paper describes the use of the marmoset monkey as an in vivo model in which the cellular and molecular regulation of angiogenesis in the ovary can be investigated and the effects of manipulation of angiogenic factors elucidated. The studies are based on quantifying changes in blood vessel area and endothelial cell proliferation, monitoring changes in expression patterns of putative angiogenic regulatory factors and targeting these factors by antagonists in vivo. Quantification of endothelial cell proliferation shows that angiogenesis commences in the pre-antral follicle, increases with follicular development and becomes intense in the early corpus luteum. Vascular endothelial growth factor (VEGF), a principal angiogenic factor, is synthesized by the developing follicle and corpus luteum. Administration of specific antagonists in vivo for selected periods of the ovulatory cycle shows that inhibition of VEGF results in a marked decrease in endothelial cell proliferation in the follicle and is accompanied by a decline in granulosa cell proliferation. Inhibition during the early or mid-luteal phase results in a marked suppression in luteal angiogenesis, failure of development of the microvascular tree and suppression of luteal function. Manipulation of angiogenesis should be a novel approach to either promoting or inhibiting the normal processes of folliculogenesis, ovulation and corpus luteum function.

Abstract 631: Nox1-Mediated CREB Promotes Gremlin1-Induced Endothelial Cell (EC) Proliferation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Daniel de Jesus ◽  
Sanghamitra Sahoo ◽  
Anastasia Gorelova ◽  
Maria Eugenia Cifuentes-Pagano ◽  
Patrick Pagano
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Critical Role ◽  
Right Heart Failure ◽  
Camp Response Element ◽  
Vascular Cell ◽  
Creb Activation ◽  
Pulmonary Arterial ◽  
Bmp Antagonist

Background: Pulmonary arterial hypertension (PAH) is a devastating, rapidly degenerating disease characterized by lung vascular cell proliferation/remodeling and elevated vascular pressure leading to right heart failure. We previously showed that BMP antagonist-Gremlin1 elicits pulmonary endothelial cell (EC) proliferation in response to hypoxia, a stimulus that recapitulates in vivo changes occurring in human PAH also leading to vascular cell proliferation and remodeling. NADPH oxidase-derived reactive oxygen species (ROS) purportedly play a critical role in PAH; yet the mechanisms by which they propagate the disease are scant. Other studies show that the cAMP response element protein (CREB) is activated by ROS and modulates cell proliferation. We postulated that Nox1-mediated CREB activation leads to Gremlin1 expression promoting human pulmonary arterial EC (HPAEC) proliferation. Method: HPAECs were subjected to 24 hrs hypoxia (1% O 2 ) vs. normoxia (21% O 2 ). Nox1, Nox2, Nox4, active CREB (pCREB), Gremlin1 and active Smads1/5/8 (pSmads) were evaluated by Western blot. Superoxide anion (O 2 •- ) changes were assessed using cytochrome C. To evaluate whether CREB binds to Gremlin1 promoter, chromatin immunoprecipitation (CHIP) was performed. Results: Hypoxia upregulated Nox1 (58% increase vs. normoxia, p<0.0001) but did not affect Nox2 and 4 levels. Hypoxia induced O 2 •- (13.6±1.5 vs. 18.3±0.6 nmol/min*mg, normoxia v. hypoxia, respectively, p<0.05). Furthermore, hypoxia increased pCREB (66% vs. normoxia, p<0.05), and Gremlin1 (39% increase vs. normoxia) whereas it decreased pSmads 1/5/8 (50% reduction vs. normoxia, p<0.05). Nox1 siRNA decreased pCREB (48% reduction vs. hypoxia alone, p=0.08). Finally, preliminary data show CREB binding to the Gremlin1 promoter. Discussion: In the present study, we found that hypoxia-induced HPAEC O 2 •- derived from Nox1 appears to mediate CREB activation, and subsequent promotion of Gremlin1 expression. Taken together, our data are consistent with CREB mediating Nox1-Gremlin1 signaling in hypoxia-induced EC proliferation.

Kallistatin Inhibits Endothelial Cell Proliferation, Migration and Adhesion in Vitro and Angiogenesis in the Ischemic Hindlimb of Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 706-707
Author(s):  
Robert Q Miao ◽  
Jun Agata ◽  
Lee Chao ◽  
Julie Chao
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Gene Delivery ◽  
Fluorescent Protein ◽  
Regional Blood Flow ◽  
Endothelial Cell Proliferation ◽  
Hek 293

P76 Kallistatin is a serine proteinase inhibitor (serpin) which has multifunctions including regulation of tissue kallikrein activity, blood pressure, inflammation and neointima hyperplasia. In this study, we investigated the potential role of kallistatin in vascular biology by studying its effects on the proliferation, migration and adhesion of cultured primary human endothelial cells in vitro, and angiogenesis in the ischemic hindlimb of rats. Purified kallistatin significantly inhibits cultured endothelial cell proliferation, migration and adhesion induced by VEGF or bFGF. To further investigate the role of kallistatin in vascular growth in vivo, we prepared adenovirus carrying the human kallistatin gene under the control of the cytomegalovirus promoter/enhancer (Ad.CMV-cHKBP). Expression of recombinant human kallistatin in HEK 293 cells transfected with Ad.CMV-cHKBP was identified by a specific ELISA. The effect of adenovirus-mediated kallistatin gene delivery on angiogenesis was evaluated in a rat model of hindlimb ischemia. Adenovirus carrying the human kallistatin or green fluorescent protein (GFP) gene were injected locally into the ischemic adductor at the time of surgery. Histological and morphometric analysis at 14 days post injection showed that adenovirus-mediated kallistatin gene delivery significantly reduced capillary density in the ischemic muscle as compared to that of control rats injected with GFP. The anti-angiogenic effect of kallistatin was associated with reduced regional blood flow in the ischemic hindlimb measured by microsphere assays. Expression of human kallistatin was identified in the injected muscle and immunoreactive human kallistatin levels were measured in the muscle and in the circulation of rats following kallistatin gene delivery. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and in vascular remodeling.

scholarly journals Prenatal inflammation impairs intestinal microvascular development through a TNF-dependent mechanism and predisposes newborn mice to necrotizing enterocolitis

2019 ◽  
Vol 317 (1) ◽  
pp. G57-G66 ◽  
Author(s):  
Xiaocai Yan ◽  
Elizabeth Managlia ◽  
Xiao-Di Tan ◽  
Isabelle G. De Plaen
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Necrotizing Enterocolitis ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Fetal Serum ◽  
Prenatal Inflammation ◽  
Vegfr2 Signaling

Prenatal inflammation is a risk factor for necrotizing enterocolitis (NEC), and it increases intestinal injury in a rat NEC model. We previously showed that maldevelopment of the intestinal microvasculature and lack of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) signaling play a role in experimental NEC. However, whether prenatal inflammation affects the intestinal microvasculature remains unknown. In this study, mouse dams were injected intraperitoneally with lipopolysaccharide (LPS) or saline at embryonic day 17. Neonatal intestinal microvasculature density, endothelial cell proliferation, and intestinal VEGF-A and VEGFR2 proteins were assessed in vivo. Maternal and fetal serum TNF concentrations were measured by ELISA. The impact of TNF on the neonatal intestinal microvasculature was examined in vitro and in vivo, and we determined whether prenatal LPS injection exacerbates experimental NEC via TNF. Here we found that prenatal LPS injection significantly decreased intestinal microvascular density, endothelial cell proliferation, and VEGF and VEGFR2 protein expression in neonatal mice. Prenatal LPS injection increased maternal and fetal serum levels of TNF. TNF decreased VEGFR2 protein in vitro in neonatal endothelial cells. Postnatal TNF administration in vivo decreased intestinal microvasculature density, endothelial cell proliferation, and VEGF and VEGFR2 protein expression and increased the incidence of severe NEC. These effects were ameliorated by stabilizing hypoxia-inducible factor-1α, the master regulator of VEGF. Furthermore, prenatal LPS injection significantly increased the incidence of severe NEC in our model, and the effect was dependent on endogenous TNF. Our study suggests that prenatal inflammation increases the susceptibility to NEC, downregulates intestinal VEGFR2 signaling, and affects perinatal intestinal microvascular development via a TNF mechanism. NEW & NOTEWORTHY This report provides new evidence that maternal inflammation decreases neonatal intestinal VEGF receptor 2 signaling and endothelial cell proliferation, impairs intestinal microvascular development, and predisposes neonatal mouse pups to necrotizing enterocolitis (NEC) through inflammatory cytokines such as TNF. Our data suggest that alteration of intestinal microvascular development may be a key mechanism by which premature infants exposed to prenatal inflammation are at risk for NEC and preserving the VEGF/VEGF receptor 2 signaling pathway may help prevent NEC development.

Lung endothelial cell proliferation in normal and pulmonary hypertensive neonatal calves

1998 ◽  
Vol 275 (3) ◽  
pp. L593-L600 ◽  
Author(s):  
Leopold Stiebellehner ◽  
James K. Belknap ◽  
Beverly Ensley ◽  
Alan Tucker ◽  
E. Christopher Orton ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Main Pulmonary Artery ◽  
Endothelial Cell Proliferation ◽  
Hemodynamic Changes ◽  
Vascular Segment ◽  
Neonatal Calves

Tremendous changes in pressure and flow occur in the pulmonary and systemic circulations after birth, and these hemodynamic changes should markedly affect endothelial cell replication. However, in vivo endothelial replication rates in the neonatal period have not been reported. To label replicating endothelial cells, we administered the thymidine analog bromodeoxyuridine to calves ∼1, 4, 7, 10, and 14 days old before they were killed. Because we expected the ratio of replicating to nonreplicating cells to vary with vascular segment, we examined the main pulmonary artery, a large elastic artery, three sizes of intrapulmonary arteries, the aorta, and the carotid artery. In normoxia for arteries < 1,500 μm, ∼27% of the endothelial cells were labeled on day 1 but only ∼2% on day 14. In the main pulmonary artery, only ∼4% of the endothelial cells were labeled on day 1 and ∼2% on day 14. In contrast, in the aorta, ∼12% of the endothelial cells were labeled on day 1 and ∼2% on day 14. In chronically hypoxic animals, only ∼14% of the endothelial cells were labeled on day 1 in small lung arteries and ∼8% were still labeled on day 14. We conclude that the postnatal circulatory adaptation to extrauterine life includes significant changes in endothelial cell proliferation that vary dramatically with time and vascular location and that these changes are altered in chronic hypoxia.

Tamoxifen inhibits endothelial cell proliferation and attenuates VEGF-mediated angiogenesis and migration in vivo

2001 ◽  
Vol 27 (8) ◽  
pp. 714-718 ◽  
Author(s):  
D.A McNamara ◽  
J Harmey ◽  
J.H Wang ◽  
E Kay ◽  
T.N Walsh ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Endothelial Cell Proliferation ◽  
And Migration

SMALL MOLECULE Flk- ANTAGONISTS INHIBIT ENDOTHELIAL CELL PROLIFERATION AND IN VIVO TUMOR GROWTH

1996 ◽  
Vol 19 (6) ◽  
pp. 466
Author(s):  
L K Shawer ◽  
G McMahon ◽  
C Tang ◽  
L Sun ◽  
H App ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Tumor Growth ◽  
Small Molecule ◽  
Endothelial Cell Proliferation
Sign in / Sign up

Export Citation Format

Share Document