Localization of VEGF and expression of its receptors flit and KDR in human placenta throughout pregnancy

Clark, Dawn E.; Smith, S. K.; Sharkey, Andrew; Charnock-Jones, D. Stephen

doi:10.1093/oxfordjournals.humrep.a019303

Cited by 270 publications

(135 citation statements)

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“…These findings are in partial agreement with those of previous investigations (Cooper et al 1995;Clark et al 1996; Cheung 1997; Shore et al 1997;Dunk and Ahmed 2001;Demir et al 2004).…”

Section: Discussionsupporting

confidence: 93%

“…Several studies have been undertaken investigating the expression of the VEGF family and its receptors in placental tissues of women with normal pregnancies (Cooper et al 1995;Clark et al 1996;Cheung 1997;Shore et al 1997;Dunk and Ahmed 2001;Demir et al 2004) and pregnancies complicated by hypertensive disorders (Cooper et al 1996;Lyall et al 1997;Cheng et al 2001;El-Salahy et al 2001;Helske et al 2001;Ranheim et al 2001;Kumazaki et al 2002;Zhou et al 2002;Tsatsaris et al 2003). However, there are some discrepancies in the data reported.…”

Section: Introductionmentioning

confidence: 99%

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Expression of vascular endothelial growth factor receptor types 1, 2 and 3 in placenta from pregnancies complicated by hypertensive disorders

Marini

Vichi

Toscano

et al. 2007

Reprod. Fertil. Dev.

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Abstract. The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) family receptors (VEGFR) in placentas from pregnancies complicated by hypertensive disorders of different clinical severity. Placental tissue from women with gestational hypertension, pre-eclampsia, pre-eclampsia with haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) and normotensive women, as a control group, was examined. Immunohistochemical techniques, reverse transcription-polymerase chain reaction and western blot were used to evaluate receptor expression. In cases with gestational hypertension, as well as in control cases, VEGFR-1 and VEGFR-3 immunoreactivity was detected in all placental components, whereas in placentas from the pre-eclampsia and pre-eclampsia with HELLP syndrome groups, VEGFR-1 and VEGFR-3 immunoreactivity was detected only in some portions of trophoblast and/or some vessels and/or clusters of stromal cells. In the control group, VEGFR-2 immunoreactivity was observed only in the vessels, whereas the hypertensive groups showed VEGF-2 immunoreactivity also in trophoblast and stromal cells. The mRNA levels of the three receptors in the group with gestational hypertension were higher with respect to those in the control group. Placentas from pregnancies with pre-eclampsia showed lowest mRNA expression levels, whereas placentas from women with pre-eclampsia plus HELLP syndrome showed higher mRNA expression levels with respect to the three other groups. Receptor protein levels were lower in pathological cases compared with levles in the control group. These findings demonstrate a dysregulation of placental expression of VEGF family receptors related to the degree of clinical severity of the hypertensive disorder.

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“…These findings are in partial agreement with those of previous investigations (Cooper et al 1995;Clark et al 1996; Cheung 1997; Shore et al 1997;Dunk and Ahmed 2001;Demir et al 2004).…”

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Expression of vascular endothelial growth factor receptor types 1, 2 and 3 in placenta from pregnancies complicated by hypertensive disorders

Marini

Vichi

Toscano

et al. 2007

Reprod. Fertil. Dev.

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show abstract

“…Less clear is the scale of change within the placenta, and yet an important factor influencing transport to the fetus is integrated development of villi and fetal vessels within them. Hypoxia-dependent foetoplacental angiogenesis during normal gestation helps to determine the pattern and scale of villous growth and maturation by regulating angiogenic growth factors and their natural receptors and antagonists [4,5,6,7,8].…”

Section: T M Mayhewmentioning

confidence: 99%

Enhanced fetoplacental angiogenesis in pre-gestational diabetes mellitus: the extra growth is exclusively longitudinal and not accompanied by microvascular remodelling

Mayhew

2002

Diabetologia

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Aims/hypothesis. Morphometric studies on pregnancies complicated by gestational diabetes mellitus have found no evidence of increased fetoplacental angiogenesis. Here, placentas from control subjects and patients with pre-gestational Type I (insulin-dependent) diabetes mellitus were used to test for differences in measures of angiogenesis and vascular remodelling. Methods. Term placentas were collected from non-diabetic subjects and well-controlled diabetic patients grouped according to duration and severity into White classes B, C, D and F/R. Tissues were obtained by uniform random sampling for position and orientation. Volumes, surface areas and lengths of peripheral villi and their capillaries were estimated stereologically. Comparisons were drawn by analysis of variance and used to interpret mechanisms of growth, villous capillarization and vessel remodelling. Results. Placentas associated with all classes of diabetes contained greater (19-45%) volumes of fetal capillaries attributable solely to increases in the combined length of capillaries (12-47%) and not to alteration of vessel cross-sectional area or perimeter. Longitudinal growth tended to increase capillarization (capillary:villus length ratios up to 19% larger) but changes were inconsistent between diabetic classes. There was no evidence of altered vascular remodelling (cross-sectional shape factors, perimeter 2 /area, were preserved). Conclusions/interpretations. In well-controlled pre-gestational diabetes, fetoplacental angiogenesis is enhanced and occurs exclusively by longitudinal growth. Differences may involve hypoxic or other metabolic effects on endothelial cells, perivascular cells and angiogenic factors. The findings differ from those previously reported in gestational diabetes. No differences were associated exclusively with the presence of diabetic complications.

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“…VEGF, Ang-1, Ang-2, and the Tie-2 receptor are expressed by cytotrophoblasts and syncytiotrophoblast as well as vascular and avascular cells within the human villous placenta [5][6][7][8][9], consistent with their proposed role upon placental vascular development. However, very little is known about the regulation of these respective angioregulatory factors within the villous placenta during human pregnancy.…”

Section: Introductionmentioning

confidence: 94%

Differential Expression of Placental Villous Angiopoietin-1 and -2 During Early, Mid and Late Baboon Pregnancy

et al. 2007

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Although vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 have important roles in angiogenesis, very little is known about the regulation of these factors in the villous placenta during human pregnancy. In the present study, to investigate whether placental expression of Ang-1, Ang-2 and VEGF was altered in a cell-specific manner with advancing baboon gestation, the mRNA levels of these growth factors were determined by RT-PCR in cells isolated by Percoll gradient centrifugation from and protein localization assessed by immunocytochemistry in the villous placenta at early (day 60), mid (day 100) and late (day 170, term is 184 days) baboon gestation. Mean (± SE) Ang-1 mRNA levels, relative to 18S rRNA, in villous syncytiotrophoblast (3.92 ± 0.68) and cytotrophoblast (1.31 ± 0.31) cell fractions were highest on day 60 of gestation, then decreased by approximately 2.5-fold (P<0.05) to 1.39 ± 0.29 and 0.49 ±0.07, respectively, on day 170. Moreover, Ang-1 mRNA levels in the villous stromal cells and Ang-2 mRNA levels in all placental villous cell fractions were similar on days 60, 100, and 170 of gestation. In contrast to Ang-1 and Ang-2, placental villous cytotrophoblast VEGF mRNA levels were increased 2.94 fold (P<0.05) between mid (0.67 ± 0.15) and late (1.97 ± 0.49) gestation. A corresponding decrease in Ang-1, absence of change in Ang-2, and increase in VEGF protein immunocytochemical expression were exhibited in placental trophoblast with advancing baboon pregnancy. Ang-1/-2 and the angiopoietin Tie-2 receptor were expressed in vascular endothelial cells of the villous placenta, indicating that these blood vessel cells are a major site of ligand-receptor interaction for angiogenesis during primate pregnancy. We conclude that there is a cell-specific differential change in placental villous trophoblast expression of VEGF, Ang-1, and Ang-2 which we propose is important in regulating angiogenesis in the villous placenta during primate pregnancy.

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Localization of VEGF and expression of its receptors flit and KDR in human placenta throughout pregnancy

Cited by 270 publications

References 0 publications

Expression of vascular endothelial growth factor receptor types 1, 2 and 3 in placenta from pregnancies complicated by hypertensive disorders

Expression of vascular endothelial growth factor receptor types 1, 2 and 3 in placenta from pregnancies complicated by hypertensive disorders

Enhanced fetoplacental angiogenesis in pre-gestational diabetes mellitus: the extra growth is exclusively longitudinal and not accompanied by microvascular remodelling

Differential Expression of Placental Villous Angiopoietin-1 and -2 During Early, Mid and Late Baboon Pregnancy

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