A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants

Ligi, Isabelle; Simoncini, Stéphanie; Tellier, Edwige; Vassallo, Paula Frizera; Sabatier, Florence; Guillet, Benjamin; Lamy, Elsa; Sarlon, Gabrielle; Quemener, Cathy; Bikfalvi, Andréas; Marcelli, M.; Pascal, Alain; Dizier, Blandine; Simeoni, Umberto; Dignat-George, Françoise; Anfosso, Francine

doi:10.1182/blood-2010-12-325142

Cited by 84 publications

(98 citation statements)

References 51 publications

(65 reference statements)

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“…Preterm birth is a pathophysiological event, often associated with combinations of stress, hypoxia, infection, and inflammation. 1,19,36 Ligi et al 19 demonstrated that the gene profile of endothelial colony-forming cells isolated from the mononuclear cell fraction obtained from cord blood, after preterm birth, exhibits a programmed shift toward increased expression of genes with antiangiogenic functions. 10 Physiologically, this was sufficient for both the cells and the cord sera to impair angiogenesis in vitro.…”

Section: Discussionmentioning

confidence: 99%

Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

et al. 2015

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Preterm-born individuals have elevated blood pressure. We tested the hypothesis that this associates with an enhanced antiangiogenic circulating profile and that this association is mediated by variations in capillary density. We studied 204 adults aged 25 years (range, 20–30 years), of which 102 had been followed up prospectively since very preterm birth (mean gestational age, 30.3±2.5 weeks) and 102 were born term to uncomplicated pregnancies. A panel of circulating biomarkers, including soluble endoglin and soluble fms-like tyrosine kinase-1, were compared between groups and related to perinatal history and adult cardiovascular risk. Associations with cardiovascular phenotype were studied in 90 individuals who had undergone detailed assessment of microvascular, macrovascular, and cardiac structure and function. Preterm-born individuals had elevations in soluble endoglin (5.64±1.03 versus 4.06±0.85 ng/mL; P <0.001) and soluble fms-like tyrosine kinase-1 (88.1±19.0 versus 73.0±15.3 pg/mL; P <0.001) compared with term-born individuals, proportional to elevations in resting and ambulatory blood pressure, as well as degree of prematurity ( P <0.05). Maternal hypertensive pregnancy disorder was associated with additional increases in soluble fms-like tyrosine kinase-1 ( P =0.002). Other circulating biomarkers, including those of inflammation and endothelial activation, were not related to blood pressure. There was a specific graded association between soluble endoglin and degree of functional and structural capillary rarefaction ( P =0.002 and P <0.001), and in multivariable analysis, there were capillary density–mediated associations between soluble endoglin and blood pressure. Preterm-born individuals exhibit an enhanced antiangiogenic state in adult life that is specifically related to elevations in blood pressure. The association seems to be mediated through capillary rarefaction and is independent of other cardiovascular structural and functional differences in the offspring.

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Section: Discussionmentioning

confidence: 99%

Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

et al. 2015

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“…The underlying mechanism that mediates the association between the perturbed fetal condition and the development of cardiovascular disease in later life has been incompletely understood. Human clinical and in vitro studies showed that the aortic intima-media layers of IUGR fetuses and neonates were thicker than those of fetuses and neonates with normal growth (5), and the endothelial progenitor cells of IUGR infants had impaired angiogenic properties and tubular formation (30). These observa- tions have suggested that the vascular systems of IUGR patients were impaired.…”

Section: Discussionmentioning

confidence: 83%

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

Inoue

Nishio

Takada

et al. 2016

The Journal of Immunology

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Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface.

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“…Furthermore, the angiogenic defect of LBW endothelial colony-forming cells was confirmed in mice by their inability to form robust capillary networks. 43 Regarding the research implications of the study, further research is needed to clarify the pathogenic links that could explain the correlation between birthweight and the development of this autoimmune disease, in particular the mechanisms that result from a complex interplay among the factors of genetic susceptibility, environmental exposure, and epigenetic modifications. On the basis of the identification of specific epigenetic mechanisms, it would be possible to develop appropriate diagnostic and therapeutic strategies as part of a personalized/precision medicine approach that would improve the clinical outcome of patients with SSc.…”

Section: Ajogorgmentioning

confidence: 99%

Fetal programming and systemic sclerosis

Donzelli

Carnesecchi

Amador

et al. 2015

American Journal of Obstetrics and Gynecology

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OBJECTIVE: This study investigated whether birthweight is linked to an increased risk of the development of systemic sclerosis. STUDY DESIGN:This was a multicenter case-control study with perinatal data that were obtained from 332 cases with systemic sclerosis and 243 control subjects. Birthweight was treated as a dichotomous variable (<2500 g vs !2500 g); low birthweight was defined as a weight <2500 g; small for gestational age was defined as birthweight <10th percentile for gestational age adjusted for sex. The relationship between systemic sclerosis and both low birthweight and small for gestational age was expressed with the crude (univariate analysis) and adjusted (multivariate analysis) odds ratio (OR). RESULTS:Significantly increased ORs were observed in the univariate analysis for low birthweight (OR, 2.59; 95% confidence interval [CI], 1.39e5.05) and small for gestational age (OR, 2.60; 95% CI, 1.34e5.32) subjects. Similarly increased risks were confirmed for both conditions in the multivariate analysis (OR, 3.93; 95% CI, 1.92e8.07; and OR, 2.58; 95% CI, 1.28e5.19), respectively. CONCLUSION: Low birthweight and small for gestational age at birth are risk factors for the adult onset of systemic sclerosis.

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A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants

Cited by 84 publications

References 51 publications

Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

Fetal programming and systemic sclerosis

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