Increased Stiffness of the Abdominal Aorta With Intrauterine Growth Restriction in the Near-Term Fetal Sheep

2012 ◽  
Author(s):  
Reuben Blair Dodson ◽  
Paul J. Rozance ◽  
Kendall S. Hunter ◽  
Virginia L. Ferguson
Keyword(s):  
Abdominal Aorta ◽  
Intrauterine Growth Restriction ◽  
Structural Changes ◽  
Epidemiological Studies ◽  
Growth Restriction ◽  
Fetal Sheep ◽  
Intrauterine Growth ◽  
Systemic Artery ◽  
Artery Stiffness ◽  
Near Term

Fetal intrauterine growth restriction (IUGR) results in increased placental resistance to blood flow, fetal hypertension and increased pulsatility [1]. These hemodynamic changes have been shown to lead to vascular remodeling in adolescents and adults [2, 3] but have received little study of its effect during this critical period of vascular formation. Epidemiological studies link IUGR to cardiovascular disease in adulthood [4], but the reason for this is not clearly understood. Here, we examine a large elastic artery for developmental alterations under hypertensive conditions. We hypothesize that fetal hypertension induces abdominal aorta (AA) stiffening in the fetal ovine model of IUGR and that the increased systemic artery stiffness is due to altered extracellular matrix (ECM) composition and structural changes.

scholarly journals Intrauterine growth restriction decreases NF-κB signaling in fetal pulmonary artery endothelial cells of fetal sheep

2018 ◽  
Vol 315 (3) ◽  
pp. L348-L359 ◽  
Author(s):  
R. Blair Dodson ◽  
Kyle N. Powers ◽  
Jason Gien ◽  
Paul J. Rozance ◽  
Gregory Seedorf ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Intrauterine Growth Restriction ◽  
Lung Diseases ◽  
Growth Restriction ◽  
Mouse Lung ◽  
Similar Degree ◽  
Fetal Sheep ◽  
Vascular Growth ◽  
Intrauterine Growth ◽  
Pulmonary Artery Endothelial Cell

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia, a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis; however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The NF-κB pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NF-κB-regulated proangiogenic targets in fetal PAEC. PAECs were isolated from the lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NF-κB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NF-κB targets. In comparison with controls, immunostaining of active NF-κB complexes, NF-κB-DNA binding, baseline expression of NF-κB subunits p65 and p50, and LPS-mediated inducible activation of NF-κB signaling were decreased in IUGR PAEC. Although pharmacological NF-κB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NF-κB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NF-κB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NF-κB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

scholarly journals Impact of diet on the persistence of early vascular remodeling and stiffening induced by intrauterine growth restriction and a maternal high-fat diet

2019 ◽  
Vol 317 (2) ◽  
pp. H424-H433 ◽  
Author(s):  
Thomas A. Miller ◽  
R. Blair Dodson ◽  
Anastasiya Mankouski ◽  
Kyle N. Powers ◽  
Yueqin Yang ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
High Fat Diet ◽  
Intrauterine Growth Restriction ◽  
Vascular Remodeling ◽  
Structural Changes ◽  
Growth Restriction ◽  
Female Rats ◽  
High Fat ◽  
Regular Diet ◽  
Intrauterine Growth

Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as postnatal day (PND) 21. The trajectory of such early vascular changes remains unknown. We hypothesized that IUGR would increase blood pressure (BP), arterial stiffness, and markers of ongoing detrimental vascular remodeling in adult rats exposed to a maternal HFD regardless of weaning diet. Adult female rats were fed either a regular diet (RD) or an HFD before mating through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either a RD or HFD through PND 60. For both control and IUGR rats, this design resulted in the following three diet groups: offspring from RD dams weaned to a RD and offspring from HFD dams weaned to a RD or to an HFD (IHH). In both males and females, only IHH increased systolic BP, but IUGR and HFD both alone and in combination increased arterial stiffness. Aortas contained fewer but thicker elastin bands in IHH rats and IUGR offspring from dams fed an HFD and weaned to a regular diet. IHH increased aortic lysl oxidase protein. In summary, the PND 21 rat mediators of vascular remodeling from IUGR and maternal HFD normalize by PND 60 while changes in elastin and arterial stiffness persist. We speculate that the longer-term risk of hypertension from dietary mediators is augmented by underlying IUGR-induced structural changes to the extracellular matrix. NEW & NOTEWORTHY We report that a combined insult of intrauterine growth restriction and maternal high-fat diet increases the risk of early cardiovascular pathology both independently and in conjunction with a continued high-fat diet in offspring.

scholarly journals Increased Hepatic Glucose Production in Fetal Sheep With Intrauterine Growth Restriction Is Not Suppressed by Insulin

Diabetes ◽  
2012 ◽  
Vol 62 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Stephanie R. Thorn ◽  
Laura D. Brown ◽  
Paul J. Rozance ◽  
William W. Hay ◽  
Jacob E. Friedman
Keyword(s):  
Intrauterine Growth Restriction ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Growth Restriction ◽  
Fetal Sheep ◽  
Intrauterine Growth ◽  
Hepatic Glucose

Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep

2001 ◽  
Vol 184 (2) ◽  
pp. 209-216 ◽  
Author(s):  
Megan L. Cock ◽  
Cheryl A. Albuquerque ◽  
Belinda J. Joyce ◽  
Stuart B. Hooper ◽  
Richard Harding
Keyword(s):  
Intrauterine Growth Restriction ◽  
Lung Development ◽  
Growth Restriction ◽  
Fetal Sheep ◽  
Intrauterine Growth ◽  
Lung Liquid ◽  
Liquid Dynamics

scholarly journals Docosahexaenoic Acid and Lactoferrin Effects on the Brain and Placenta in a Rabbit Model of Intrauterine Growth Restriction 

2021 ◽  
Author(s):  
Miriam Illa ◽  
Laura Pla ◽  
Carla Loreiro ◽  
Cristina Miranda ◽  
Montse Mayol ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Intrauterine Growth Restriction ◽  
Structural Changes ◽  
Rabbit Model ◽  
Perinatal Outcomes ◽  
Growth Restriction ◽  
Functional Evaluation ◽  
Neurobehavioral Performance ◽  
Intrauterine Growth ◽  
The Brain

Abstract Intrauterine growth restriction (IUGR) is associated with suboptimal perinatal outcomes and neurodevelopment in the offspring. We hypothesize that prenatal supplementation with docosahexaenoic acid (DHA) or lactoferrin (Lf) would ameliorate these consequences. At 25 days of gestation, IUGR was surgically induced in pregnant rabbits, which were randomized as follows: no treatment, or DHA or Lf administration. DHA or Lf were administrated orally once per day. Five days later, animals were delivered obtaining controls, untreated IUGR, IUGR treated with DHA and IUGR treated with Lf, and the associated placentas. At postnatal day 1, a functional evaluation was performed and, thereafter, brains were obtained. Neuronal arborization in the prefrontal cortex and the density of pre-oligodendrocytes in the corpus callosum were then evaluated. Untreated IUGR pups presented a higher percentage of stillbirth, lower birth weight, and poorer neurobehavioral performance in comparison with control pups, and these are associated with structural changes in brain and placenta. Regarding treated IUGR animals, although no significant improvements were detected in perinatal data, functional and structural effects were observed in either the brain or the placenta. DHA and Lf supplements in a rabbit model of IUGR were related to neurodevelopmental improvements and an amelioration of the placental changes.

Intrauterine growth restriction promotes vascular remodelling following carotid artery ligation in rats

2012 ◽  
Vol 123 (7) ◽  
pp. 437-444 ◽  
Author(s):  
Carlos Menendez-Castro ◽  
Nada Cordasic ◽  
Matthias Schmid ◽  
Fabian Fahlbusch ◽  
Wolfgang Rascher ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Intrauterine Growth Restriction ◽  
Later Life ◽  
Epidemiological Studies ◽  
Growth Restriction ◽  
Vascular Remodelling ◽  
Artery Ligation ◽  
Intrauterine Growth ◽  
Carotid Artery Ligation ◽  
Increased Risk

Epidemiological studies revealed an association between IUGR (intrauterine growth restriction) and an increased risk of developing CVDs (cardiovascular diseases), such as atherosclerosis or hypertension, in later life. Whether or not IUGR contributes to the development of atherosclerotic lesions, however, is unclear. We tested the hypothesis that IUGR aggravates experimentally induced vascular remodelling. IUGR was induced in rats by maternal protein restriction during pregnancy (8% protein diet). To detect possible differences in the development of vascular injury, a model of carotid artery ligation to induce vascular remodelling was applied in 8-week-old intrauterine-growth-restricted and control rat offspring. Histological and immunohistochemical analyses were performed in the ligated and non-ligated carotid arteries 8 weeks after ligation. IUGR alone neither caused overt histological changes nor significant dedifferentiation of VSMCs (vascular smooth muscle cells). After carotid artery ligation, however, neointima formation, media thickness and media/lumen ratio were significantly increased in rats after IUGR compared with controls. Moreover, dedifferentiation of VSMCs and collagen deposition in the media were more prominent in ligated carotids from rats after IUGR compared with ligated carotids from control rats. We conclude that IUGR aggravates atherosclerotic vascular remodelling induced by a second injury later in life.

scholarly journals Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction

2010 ◽  
Vol 298 (4) ◽  
pp. E770-E778 ◽  
Author(s):  
Rafael A. Leos ◽  
Miranda J. Anderson ◽  
Xiaochuan Chen ◽  
Juliana Pugmire ◽  
K. Arbor Anderson ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Intrauterine Growth Restriction ◽  
Adrenergic Receptor ◽  
Plasma Insulin ◽  
Placental Insufficiency ◽  
Growth Restriction ◽  
Receptor Expression ◽  
Plasma Norepinephrine ◽  
Fetal Sheep ◽  
Intrauterine Growth

In this study, we examined chronic norepinephrine suppression of insulin secretion in sheep fetuses with placental insufficiency-induced intrauterine growth restriction (IUGR). Glucose-stimulated insulin secretion (GSIS) was measured with a square-wave hyperglycemic clamp in the presence or absence of adrenergic receptor antagonists phentolamine (α) and propranolol (β). IUGR fetuses were hypoglycemic and hypoxemic and had lower GSIS responsiveness ( P ≤ 0.05) than control fetuses. IUGR fetuses also had elevated plasma norepinephrine (3,264 ± 614 vs. 570 ± 86 pg/ml; P ≤ 0.05) and epinephrine (164 ± 32 vs. 60 ± 12 pg/ml; P ≤ 0.05) concentrations. In control fetuses, adrenergic inhibition increased baseline plasma insulin concentrations (1.7-fold, P ≤ 0.05), whereas during hyperglycemia insulin was not different. A greater ( P ≤ 0.05) response to adrenergic inhibition was found in IUGR fetuses, and the average plasma insulin concentrations increased 4.9-fold at baseline and 7.1-fold with hyperglycemia. Unlike controls, basal plasma glucose concentrations fell ( P ≤ 0.05) with adrenergic antagonists. GSIS responsiveness, measured by the change in insulin, was higher (8.9-fold, P ≤ 0.05) in IUGR fetuses with adrenergic inhibition than controls (1.8-fold, not significant), showing that norepinephrine suppresses insulin secretion in IUGR fetuses. Strikingly, in IUGR fetuses, adrenergic inhibition resulted in a greater GSIS responsiveness, because β-cell mass was 56% lower and the maximal stimulatory insulin response tended ( P < 0.1) to be higher than controls. This persistent norepinephrine suppression appears to be partially explained by higher mRNA concentrations of adrenergic receptors α1D, α2A, and α2B in a cohort of fetuses that were naïve to the antagonists. Therefore, norepinephrine suppression of insulin secretion was maintained, in part, by upregulating adrenergic receptor expression, but the β-cells also appeared to compensate with enhanced GSIS. These findings may begin to explain why IUGR infants have a propensity for increased glucose requirements if norepinephrine is suddenly decreased after birth.

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