This study examined perturbed aortic development and subsequent wall stiffening as a mechanism for programming of cardiovascular disease. Placental insufficiency was induced in pregnant guinea pigs at mid-gestation by uterine artery ligation. Near term, fetuses were sacrificed and defined as normal birth weight (NBW), low birth weight (LBW) and intrauterine growth restricted (IUGR). Additional animals were allowed to pup and offspring sacrificed in adulthood. Collagen and elastin content of aortae were analyzed using Sirius Red and Orcein staining, respectively. Immunofluorescence was used for detection of α- actin and non-muscle myosin heavy chain (MHC-B), a marker of synthetic-type VSMCs. Ex-vivo generation of length-tension curves was performed with aortic rings from adult offspring. Relative elastic fibre content was decreased by 10% in SGA and 14% in IUGR, compared to NBW fetuses. In adulthood, relative elastic fibre content was 51% lower in LBW vs. NBW and the number of elastic laminae adjusted for wall thickness was 25% lower in LBW (p < .01).The percent area stained for MHC-B was 6-fold higher in LBW vs. NBW fetuses (p < .0001) and 3-fold higher in LBW vs. NBW adult offspring (p < .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 < .05). Thus, aortic wall stiffening in adulthood can be traced to a subtle offset in ECM composition established under suboptimal intrauterine conditions that is amplified postnatally by the synthetic activity of embryonic VSMCs.
- Copyright © 2011, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology