Decrease and Senescence of Endothelial Progenitor Cells in Patients with Preeclampsia

Sugawara, Junichi; Mitsui-Saito, Minori; Hayashi, Chika; Hoshiai, Tetsuro; Senoo, Masato; Chisaka, Hiroshi; Yaegashi, Nobuo; Okamura, Koji

doi:10.1210/jc.2005-0532

Cited by 105 publications

(31 citation statements)

References 17 publications

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“…Their dysfunction represents a risk factor for cardiovascular disease [27]. Previous studies of endothelial progenitor cells with hematopoietic (non-ECFC) characteristics (CD133 + and/or CD45 + ) found lower circulating numbers and reduced colony-forming ability in PE compared to control maternal blood samples [12], [13]. This implicates a source of maternal endothelial dysfunction by lessening endothelial repair and vasculogenic capacity.…”

Section: Discussionmentioning

confidence: 97%

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Vitamin D Antagonizes Negative Effects of Preeclampsia on Fetal Endothelial Colony Forming Cell Number and Function

et al. 2014

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ContextEndothelial 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.ObjectiveWe 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, PatientsThis 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 MeasuresTime 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.ResultsThe 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.ConclusionFetal 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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Section: Discussionmentioning

confidence: 97%

“…They are involved in feto-placental vasculogenesis [9], which is disturbed in women with PE [10]. Although there is evidence that maternal and fetal (umbilical cord) circulating EPCs of hematopoietic lineage are reduced in number and function during PE [11], [12], [13], data on ECFCs are presently rare.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Antagonizes Negative Effects of Preeclampsia on Fetal Endothelial Colony Forming Cell Number and Function

et al. 2014

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“…However, alterations with long-term impact on the neurovascular compartment might occur earlier during the peripartum period. Respectively, human studies have shown a significant increase in the number of circulating EPCs with the progression of pregnancy [75], an effect that was absent in women with preeclampsia [76, 77]. This is an important finding, as the peripartum-associated changes in EPCs and the microvasculature of the PVN might play an important role in enhanced availability of the neurohypophyseal hormones AVP and OXT during the peripartum period by increasing their cytoplasmatic transport from the luminal to the abdominal side of the membrane.…”

Section: Structural Functional and Molecular Plasticity Of The Bmentioning

confidence: 99%

The Maternal Brain: An Organ with Peripartal Plasticity

et al. 2014

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The time of pregnancy, birth, and lactation, is characterized by numerous specific alterations in several systems of the maternal body. Peripartum-associated changes in physiology and behavior, as well as their underlying molecular mechanisms, have been the focus of research since decades, but are still far from being entirely understood. Also, there is growing evidence that pregnancy and lactation are associated with a variety of alterations in neural plasticity, including adult neurogenesis, functional and structural synaptic plasticity, and dendritic remodeling in different brain regions. All of the mentioned changes are not only believed to be a prerequisite for the proper fetal and neonatal development, but moreover to be crucial for the physiological and mental health of the mother. The underlying mechanisms apparently need to be under tight control, since in cases of dysregulation, a certain percentage of women develop disorders like preeclampsia or postpartum mood and anxiety disorders during the course of pregnancy and lactation. This review describes common peripartum adaptations in physiology and behavior. Moreover, it concentrates on different forms of peripartum-associated plasticity including changes in neurogenesis and their possible underlying molecular mechanisms. Finally, consequences of malfunction in those systems are discussed.

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“…Despite ongoing study of the identity of these cells, multiple studies in adults demonstrate that a reduction in the circulating numbers of CFU-ECs and CPCs correlate with increased vascular disease risk, 14,16,23,24 suggesting that rare populations of circulating cells have an important role in protecting from vascular morbidities. However, limited studies have been conducted in children or young adults to examine whether a reduction in CPCs is present early in disease and whether alterations in circulating progenitor subpopulations correlate with a measure of vascular dysfunction.…”

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confidence: 99%

Endothelial Abnormalities in Adolescents with Type 1 Diabetes: A Biomarker for Vascular Sequelae?

DiMeglio

Tosh

Saha

et al. 2010

The Journal of Pediatrics

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Objective To evaluate whether counts of circulating colony forming unit-endothelial cells (CFU-ECs), cells co-expressing CD34, CD133, and CD31 (CD34+CD133+CD31+), and CD34+CD45− cells are altered in adolescents with type 1 diabetes and if the changes in counts correlate with endothelial dysfunction. Study design Adolescents with diabetes (ages 18 to 22 years) and race- and sex-matched control subjects were studied. We assessed circulating CFU-ECs, using colony assays, and CD34+CD133+CD31+ and CD34+CD45− cells, using poly-chromatic flow cytometry. CFU-ECs and CD34+CD133+CD31+ are hematopoietic-derived progenitors that inversely correlate with cardiovascular risk in adults. CD34+CD45− cells are enriched for endothelial cells with robust vasculogenic potential. Vascular reactivity was tested by laser Doppler iontophoresis. Results Subjects with diabetes had lower CD34+CD133+CD31+ cells, a trend toward reduced CFU-ECs, and increased CD34+CD45− cells compared with control subjects. Endothelium-dependent vasodilation was impaired in subjects with diabetes, which correlated with reductions in circulating CD34+CD133+CD31+ cells. Conclusions Long-term sequelae of type 1 diabetes include vasculopathies. Endothelial progenitor cells promote vascular health by facilitating endothelial integrity and function. Lower CD34+CD133+CD31+ cells may be a harbinger of future macrovascular disease risk. Higher circulating CD34+CD45− cells may reflect ongoing endothelial damage. These cells are potential biomarkers to guide therapeutic interventions to enhance endothelial function and to prevent progression to overt vascular disease.

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Decrease and Senescence of Endothelial Progenitor Cells in Patients with Preeclampsia

Abstract: Depletion and cellular aging of EPCs in patients with preeclampsia might be associated with endothelial dysfunction and could be affected by systemic inflammation.

Cited by 105 publications

References 17 publications

Vitamin D Antagonizes Negative Effects of Preeclampsia on Fetal Endothelial Colony Forming Cell Number and Function

Vitamin D Antagonizes Negative Effects of Preeclampsia on Fetal Endothelial Colony Forming Cell Number and Function

The Maternal Brain: An Organ with Peripartal Plasticity

Endothelial Abnormalities in Adolescents with Type 1 Diabetes: A Biomarker for Vascular Sequelae?

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