title: Central stiffening in adulthood linked to aberrant aortic remodeling under suboptimal intrauterine conditions.
abstract: This study examined perturbed aortic development and subsequent wall stiffening as a link to later cardiovascular disease. Placental insufficiency was induced in pregnant guinea pigs at midgestation by uterine artery ligation. Near term, fetuses were killed and defined as normal birth weight (NBW), low birth weight (LBW), and intrauterine growth restricted (IUGR). Offspring were classified according to birth weight and killed in adulthood. Collagen and elastin content of aortas were analyzed using Sirius red and orcein staining, respectively. Immunofluorescence was used for detection of α-actin and nonmuscle myosin heavy chain (MHC-B), a marker of synthetic-type vascular smooth muscle cells (VSMCs). Ex vivo generation of length-tension curves was performed with aortic rings from adult offspring. Relative elastic fiber content was decreased by 10% in LBW and 14% in IUGR compared with NBW fetuses. In adulthood, relative elastic fiber content was 51% lower in LBW vs. NBW, and the number of elastic laminae adjusted for wall thickness was 25% lower in LBW (P < 0.01). The percent area stained for MHC-B was sixfold higher in LBW vs. NBW fetuses (P < 0.0001) and threefold higher in LBW vs. NBW adult offspring (P < 0.05). The increase in MHC-B in LBW offspring concurred with a 41% increase in total collagen content and a 33 and 56% increase in relative and total α-actin content, respectively (P < 0.05). Thus aortic wall stiffening in adulthood can be traced to altered matrix composition established under suboptimal intrauterine conditions that is amplified postnatally by the activity of synthetic VSMCs.
authors: Department of Physiology and Pharmacology, Robarts Research Institute, The University of Western Ontario, London, Ontario Canada. Jathomps@uwo.ca
authors: Jennifer A
authors: JA
authors: Thompson
authors: Robert
authors: R
authors: Gros
authors: Bryan S
authors: BS
authors: Richardson
authors: Karolina
authors: K
authors: Piorkowska
authors: Timothy R H
authors: TR
authors: Regnault
mesh_terms: D000818:Animals; D001011:Aorta / Q000254:growth & development* / Q000473:pathology*; D001018:Aortic Diseases / Q000196:embryology* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation; D006168:Guinea Pigs; D010927:Placental Insufficiency / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy
chemical_list: D003094:Collagen; D004549:Elastin