Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep

Dodson, R. Blair; Rozance, Paul J.; Petrash, Carson C.; Hunter, Kendall S.; Ferguson, Virginia L.

doi:10.1152/ajpheart.00472.2013

Cited by 40 publications

(41 citation statements)

References 44 publications

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“…Two other studies have also noted depletion in the number of elastin fibers after LVAD support. 3,4 Alterations of collagen and elastin are known to directly affect vessel compliance, 10,11 and the histological findings of this study are likely reflected in the mechanical changes of differences in vessel compliance.…”

Section: Discussionmentioning

confidence: 74%

Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices

Ambardekar

Hunter

Babu

et al. 2015

Circ: Heart Failure

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Background— The effects of nonpulsatile flow on the aorta are unknown. Our aim was to examine the structure of the aorta from patients with continuous-flow left ventricular assist devices (LVADs) and directly measure aortic wall composition and stiffness. Methods and Results— Age-matched aortic wall samples were collected from consecutive patients with heart failure (HF) at the time of transplantation and compared with nonfailing donor hearts. An unbiased stereological approach was used to quantify aortic morphometry and composition, and biomechanical testing was performed to determine the stress–strain relationship of the vessel. Data were obtained from 4 patients without a left ventricular assist device (HF group: mean age, 58.3±8.0 years), 7 patients with a continuous-flow LVAD (HF+LVAD group: mean, 57.7±5.6 years), and 3 nonfailing donors (mean, 53.3±12.9 years). Compared with HF, the aortic walls from HF+LVAD had an increase in wall thickness, collagen, and smooth muscle content accompanied by a reduction in elastin and mucinous ground-substance content. Stress–strain curves from the aortas revealed increased vessel stiffness in HF+LVAD compared with HF and nonfailing. The physiological modulus of the aorta progressively stiffened from 74.3±5.5 kPa in the nonfailing to 134.4±35.0 kPa in the HF to 201.7±36.4kPa in the HF+LVAD groups ( P <0.001). Conclusions— Among continuous-flow LVAD patients without aortic valve opening, there are changes in the structure and composition of the aorta as well as an increase in aortic wall stiffness compared with age-matched HF patients and nonfailing donors. Further studies examining the role of nonpulsatile blood flow on aortic function and the potential resultant systemic sequelae are needed.

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Section: Discussionmentioning

confidence: 74%

Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices

Ambardekar

Hunter

Babu

et al. 2015

Circ: Heart Failure

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“…Comparable effects of FGR on aorta remodeling have been reported in experimental models of FGR in sheep and guinea pigs (Thompson et al, 2011; Dodson et al, 2014). However, there is no clarity whether these structural alterations represent common changes in the entire circulatory system or are territory-specific.…”

Section: Introductionmentioning

confidence: 82%

Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus)

et al. 2017

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Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs.Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining.Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05).Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease.

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“…Signs of vascular remodelling of systemic arteries have been found in both human and animal studies of IUGR [25,26,27,28,29,30,31,32,33,34]. It is thought that this vascular remodelling process is caused by the systemic haemodynamic changes seen in IUGR, which alter shear stress and wall tension [35].…”

Section: Potential Consequences Of Prolonged Brain-sparingmentioning

confidence: 99%

Brain-Sparing in Intrauterine Growth Restriction: Considerations for the Neonatologist

2015

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Intrauterine growth restriction (IUGR) is most commonly caused by placental insufficiency, in response to which the fetus adapts its circulation to preserve oxygen and nutrient supply to the brain (‘brain-sparing'). Currently, little is known about the postnatal course and consequences of this antenatal adaptation of the cerebral circulation. The altered cerebral haemodynamics may persist after birth, which would imply a different approach with regard to cerebral monitoring and clinical management of IUGR preterm neonates than their appropriately grown peers. Few studies are available with regard to this topic, and the small body of evidence shows controversy. This review discusses the cerebral circulatory adaptations of IUGR fetuses and appraises the available literature on their postnatal cerebral circulation with potential clinical consequences.

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Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep

Cited by 40 publications

References 44 publications

Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices

Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices

Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus)

Brain-Sparing in Intrauterine Growth Restriction: Considerations for the Neonatologist

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