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

Abstract

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.

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

“…) as well as an increased stiffness, contractile force and media thickness (Canas et al . ). These changes are also observed in femoral resistance arteries (Canas et al .…”

“…These changes are also observed in femoral resistance arteries (Canas et al . ). Additionally, these fetal vessels have a decreased NO‐dependent relaxation that is mainly related with an impaired endothelial function (Herrera et al .…”

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

“…Additionally, an impaired foetal growth in humans is associated with vascular remodelling in the aorta at birth, as well as an increased aortic stiffness at childhood . Recent reports show that growth‐restricted guinea‐pig foetuses have an impaired NOS‐dependent relaxation in systemic and umbilical arteries which occurs in parallel with pro‐constrictive vascular remodelling in the aorta and femoral arteries, but not in the carotid artery . In this study, FGR adult guinea‐pigs showed an increased in vivo femoral vascular resistance with no diurnal variability, but a normal resistance in the carotid artery.…”

“…Vessel segments of 2 mm of carotid and femoral arteries were mounted in a wire myograph for stretch‐stress analysis as previously reported . The passive response measurements consists in to hold by hooks a vessel ring, and subject the sample to a radial elongation.…”

“…For the determination of residual stress in the different arteries studied, opening angle measurements in vessels rings were performed as reported . The opening angle was used to measure the angle (α) subtended by the ends after making a radial cut of a circular segment of the artery.…”