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PMID: 23154756 Published · ppublish English Journal Article

Increased arterial stiffness and extracellular matrix reorganization in intrauterine growth-restricted fetal sheep.

Pediatric research ·Vol. 73 ·No. 2 ·2013-02-00 ·Pages 147-54

Dodson RB, Rozance PJ, Fleenor BS, Petrash CC, Shoemaker LG, Hunter KS, Ferguson VL

Abstract

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. 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. 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. 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.

MeSH Terms
Animals Carotid Arteries/metabolism,pathology,physiopathology Cell Proliferation Collagen/metabolism Compliance Disease Models, Animal Elastin/metabolism Extracellular Matrix/metabolism,pathology Female Fetal Growth Retardation/metabolism,pathology,physiopathology Gestational Age Glycosaminoglycans/metabolism Hypertension/metabolism,physiopathology Male Pregnancy Sheep Umbilical Arteries/metabolism,pathology,physiopathology Vascular Stiffness
Chemicals
Glycosaminoglycans Collagen Elastin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dodson Reuben Blair
Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, Colorado, USA.
Rozance Paul J
Fleenor Bradley S
Petrash Carson C
Shoemaker Lauren G
Hunter Kendall S
Ferguson Virginia L
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Article Info
Journal
Pediatric research
Abbr.
Pediatr Res
ISSN
1530-0447
DOI
10.1038/pr.2012.156
Published
2013-02-00
Epub
2012-00-15
Pages
147-54
Language
English
Region
United States
NLM ID
0100714
PMCID
PMC3742323
Subset
IM
Grants
NICHD NIH HHS · K08 HD060688 · United States
NHLBI NIH HHS · K25 HL094749 · United States
NIDDK NIH HHS · R01 DK088139 · United States
NHLBI NIH HHS · R01 HL114887 · United States
External Links
PubMed source DOI: 10.1038/pr.2012.156 PMC Full Text View journal details
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