title: Increased arterial stiffness and extracellular matrix reorganization in intrauterine growth-restricted fetal sheep.
abstract: BACKGROUND
  Fetal intrauterine growth restriction (IUGR) results in increased placental resistance to blood flow, fetal hypertension, and increased pulsatility stresses shown to lead to vascular remodeling. We tested our hypothesis that IUGR causes decreased compliance in the carotid and umbilical arteries due to altered extracellular matrix (ECM) composition and structure.
  
  
  METHODS
  A sheep model of placental insufficiency-induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Umbilical and carotid arteries from near-term fetuses were tested with pressure-diameter measurements to compare passive compliance in control and PI-IUGR tissues. ECM composition was measured via biochemical assay, and the organization was determined by using histology and second-harmonic generation imaging.
  
  
  RESULTS
  We found that PI-IUGR increased arterial stiffness with increased collagen engagement, or transition stretch. PI-IUGR carotid arteries exhibited increased collagen and elastin quantity, and PI-IUGR umbilical arteries exhibited increased sulfated glycosaminoglycans. Histomorphology showed altered collagen-to-elastin ratios with altered cellular proliferation. Increased stiffness indicates altered collagen-to-elastin ratios with less elastin contribution leading to increased collagen engagement.
  
  
  CONCLUSIONS
  Because vessel stiffness is a significant predictor in the development of hypertension, disrupted ECM deposition in IUGR provides a potential link between IUGR and adult hypertension.
authors.affiliation: Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, Colorado, USA.
authors.forename: Reuben Blair
authors.initials: RB
authors.lastname: Dodson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Fleenor
authors.forename: Carson C
authors.initials: CC
authors.lastname: Petrash
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Shoemaker
authors.forename: Kendall S
authors.initials: KS
authors.lastname: Hunter
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D003187:Compliance; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005865:Gestational Age; D006025:Glycosaminoglycans / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D012756:Sheep; D014469:Umbilical Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D059289:Vascular Stiffness
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen; D004549:Elastin