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Vitamin D antagonizes negative effects of preeclampsia on fetal endothelial colony forming cell number and function.

von Versen-Höynck F, Brodowski L, Dechend R, Myerski AC, Hubel CA - PLoS ONE (2014)

Bottom Line: VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3.Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional.Vitamin D3 had rescuing effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Gynecology Research Unit, Hannover Medical School, Hannover, Germany.

ABSTRACT

Context: Endothelial dysfunction is a primary feature of preeclampsia, a pregnancy complication associated with an increased future cardiovascular risk for mother and offspring. Endothelial colony forming cells (ECFC) are endothelial progenitor cells that participate in vasculogenesis and endothelial repair.

Objective: We hypothesized that the number and functional properties of fetal cord blood-derived ECFCs are reduced in preeclampsia compared to uncomplicated pregnancy (controls), and asked if adverse effects of preeclampsia on ECFC function are reversed by 1,25 (OH)2 vitamin D3.

Design, setting, patients: This was a nested, case-control study. Forty women with uncomplicated pregnancy and 33 women with PE were recruited at Magee-Womens Hospital (USA) or at Hannover Medical School (Germany).

Main outcome measures: Time to ECFC colony appearance in culture, and number of colonies formed, were determined. Functional abilities of ECFCs were assessed in vitro by tubule formation in Matrigel assay, migration, and proliferation. ECFC function was tested in the presence or absence of 1,25 (OH)2 vitamin D3, and after vitamin D receptor (VDR) or VEGF signaling blockade.

Results: The number of cord ECFC colonies was lower (P = 0.04) in preeclampsia compared to controls. ECFCs from preeclampsia showed reduced proliferation (P<0.0001), formed fewer tubules (P = 0.02), and migrated less (P = 0.049) than control. Vitamin D3 significantly improved preeclampsia ECFC functional properties. VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3.

Conclusion: Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional. Vitamin D3 had rescuing effects. This may have implications for the increased cardiovascular risk associated with preeclampsia.

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Effect of preeclampsia (PE) and 1,25(OH)2 vitamin D3 on ECFC migration.ECFCs of uncomplicated (control) and PE pregnancies were cultured in endothelial basal medium (EBM) +2% FBS and treated with or without 1 nM or 10 nM 1,25(OH)2 vitamin D3. A: The migration of ECFCs into the scratch wound was assessed after incubation for 8 h. Results represent mean ±SEM percent wound filling, n = 8. *P<0.05 vs. untreated control or (as indicated by horizontal lines above the vertical bars) vs. untreated PE. B: Representative images of ECFC monolayers with scratch wounds at 0 h (a, c) and 8 h (b, d) of incubation of control (a, b) and preeclamptic pregnancies (c, d).
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pone-0098990-g002: Effect of preeclampsia (PE) and 1,25(OH)2 vitamin D3 on ECFC migration.ECFCs of uncomplicated (control) and PE pregnancies were cultured in endothelial basal medium (EBM) +2% FBS and treated with or without 1 nM or 10 nM 1,25(OH)2 vitamin D3. A: The migration of ECFCs into the scratch wound was assessed after incubation for 8 h. Results represent mean ±SEM percent wound filling, n = 8. *P<0.05 vs. untreated control or (as indicated by horizontal lines above the vertical bars) vs. untreated PE. B: Representative images of ECFC monolayers with scratch wounds at 0 h (a, c) and 8 h (b, d) of incubation of control (a, b) and preeclamptic pregnancies (c, d).

Mentions: With scratch wound area filling expressed as percent relative to untreated, uncomplicated pregnancy ECFCs (control, 100%), the migration of PE ECFCs was significantly impaired (66±9, P = 0.04), (Figure 2 A, B). 1,25(OH)2 vitamin D3 improved ECFC migration in both pregnancy outcome groups. At 1 nM (118±8, P = 0.04) or 10 nM (142±24, P = 0.02) the migration of uncomplicated pregnancy ECFCs was significantly stimulated. Expressed as percent relative to untreated PE (100%), migration into the scratch wound of PE ECFCs was also significantly higher after treatment with 1 nM (163±16, P = 0.01) and 10 nM (188±37, P = 0.02) 1,25(OH)2 vitamin D3. Therefore, vitamin D restored ECFC migration derived from PE pregnancies such that there was no significant between-group difference after treatment with 1 nM (P = 0.4) or 10 nM (P = 0.3) 1,25(OH)2 vitamin D3.


Vitamin D antagonizes negative effects of preeclampsia on fetal endothelial colony forming cell number and function.

von Versen-Höynck F, Brodowski L, Dechend R, Myerski AC, Hubel CA - PLoS ONE (2014)

Effect of preeclampsia (PE) and 1,25(OH)2 vitamin D3 on ECFC migration.ECFCs of uncomplicated (control) and PE pregnancies were cultured in endothelial basal medium (EBM) +2% FBS and treated with or without 1 nM or 10 nM 1,25(OH)2 vitamin D3. A: The migration of ECFCs into the scratch wound was assessed after incubation for 8 h. Results represent mean ±SEM percent wound filling, n = 8. *P<0.05 vs. untreated control or (as indicated by horizontal lines above the vertical bars) vs. untreated PE. B: Representative images of ECFC monolayers with scratch wounds at 0 h (a, c) and 8 h (b, d) of incubation of control (a, b) and preeclamptic pregnancies (c, d).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4044051&req=5

pone-0098990-g002: Effect of preeclampsia (PE) and 1,25(OH)2 vitamin D3 on ECFC migration.ECFCs of uncomplicated (control) and PE pregnancies were cultured in endothelial basal medium (EBM) +2% FBS and treated with or without 1 nM or 10 nM 1,25(OH)2 vitamin D3. A: The migration of ECFCs into the scratch wound was assessed after incubation for 8 h. Results represent mean ±SEM percent wound filling, n = 8. *P<0.05 vs. untreated control or (as indicated by horizontal lines above the vertical bars) vs. untreated PE. B: Representative images of ECFC monolayers with scratch wounds at 0 h (a, c) and 8 h (b, d) of incubation of control (a, b) and preeclamptic pregnancies (c, d).
Mentions: With scratch wound area filling expressed as percent relative to untreated, uncomplicated pregnancy ECFCs (control, 100%), the migration of PE ECFCs was significantly impaired (66±9, P = 0.04), (Figure 2 A, B). 1,25(OH)2 vitamin D3 improved ECFC migration in both pregnancy outcome groups. At 1 nM (118±8, P = 0.04) or 10 nM (142±24, P = 0.02) the migration of uncomplicated pregnancy ECFCs was significantly stimulated. Expressed as percent relative to untreated PE (100%), migration into the scratch wound of PE ECFCs was also significantly higher after treatment with 1 nM (163±16, P = 0.01) and 10 nM (188±37, P = 0.02) 1,25(OH)2 vitamin D3. Therefore, vitamin D restored ECFC migration derived from PE pregnancies such that there was no significant between-group difference after treatment with 1 nM (P = 0.4) or 10 nM (P = 0.3) 1,25(OH)2 vitamin D3.

Bottom Line: VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3.Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional.Vitamin D3 had rescuing effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Gynecology Research Unit, Hannover Medical School, Hannover, Germany.

ABSTRACT

Context: Endothelial dysfunction is a primary feature of preeclampsia, a pregnancy complication associated with an increased future cardiovascular risk for mother and offspring. Endothelial colony forming cells (ECFC) are endothelial progenitor cells that participate in vasculogenesis and endothelial repair.

Objective: We hypothesized that the number and functional properties of fetal cord blood-derived ECFCs are reduced in preeclampsia compared to uncomplicated pregnancy (controls), and asked if adverse effects of preeclampsia on ECFC function are reversed by 1,25 (OH)2 vitamin D3.

Design, setting, patients: This was a nested, case-control study. Forty women with uncomplicated pregnancy and 33 women with PE were recruited at Magee-Womens Hospital (USA) or at Hannover Medical School (Germany).

Main outcome measures: Time to ECFC colony appearance in culture, and number of colonies formed, were determined. Functional abilities of ECFCs were assessed in vitro by tubule formation in Matrigel assay, migration, and proliferation. ECFC function was tested in the presence or absence of 1,25 (OH)2 vitamin D3, and after vitamin D receptor (VDR) or VEGF signaling blockade.

Results: The number of cord ECFC colonies was lower (P = 0.04) in preeclampsia compared to controls. ECFCs from preeclampsia showed reduced proliferation (P<0.0001), formed fewer tubules (P = 0.02), and migrated less (P = 0.049) than control. Vitamin D3 significantly improved preeclampsia ECFC functional properties. VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3.

Conclusion: Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional. Vitamin D3 had rescuing effects. This may have implications for the increased cardiovascular risk associated with preeclampsia.

Show MeSH
Related in: MedlinePlus