Increased elastic tissue defect formation in the growth restricted brown Norway rat: A potential link between in utero condition and cardiovascular disease

Abstract

Low birth weight for gestational age has been epidemiologically linked to cardiovascular mortality and morbidity in adult life. This study aimed to determine whether in utero growth restriction influences an early feature of atherosclerotic pathology; disruption of the aortic internal elastic lamina (IEL) in the adult Brown Norway (BN) rat. In utero growth restriction was induced by bilateral uterine artery ligation on day 18 of gestation, thereby decreasing newborn BN pup weight by approximately 14%. Restriction surgery significantly increased aortic IEL defect number at 8 wk of age in both sexes compared with no surgery animals (p < 0.002). At 16 wk of age placental restriction surgery significantly increased the number of defects in males compared with both no surgery and sham surgery control groups (p < 0.001). The total number of IEL defects was significantly correlated with several postnatal growth rate parameters, including 72-h postpartum weight. Neither blood pressure was significantly different between treatment groups, nor was it correlated with body weight or IEL defect numbers. The findings of this study seem to support the fetal origins of adult disease hypothesis, by demonstrating that a moderate growth restricting insult dramatically increases aortic elastic tissue defect formation via an apparently blood pressure-independent mechanism. ABBREVIATIONS. Copyright © 2008 International Pediatric Research Foundation, Inc.