Abstract 349: Fetal Growth Restriction Is A Risk Of Vascular Remodeling

Abstract

Objects: A number of studies suggest that fetal growth restriction (FGR) promotes a risk of cardiovascular disease and metabolic disorders. However, it has not been well assessed whether FGR would be involved in the exaggeration of vascular remodeling. We investigated the effect of FGR on inflammatory vascular remodeling using cuff- induced vascular injury mouse model. Methods: Dams (C57BL/6J strain mice) were fed with an isocaloric diet containing 20% protein (normal protein; NP) or 8% protein (low protein; LP) from 10 weeks of ages. At the day of delivery, all dams were returned to the NP diet. After weaning, offspring were fed with the NP diet. Vascular injury was induced by polyethylene cuff placement around the femoral artery in offspring at 10 weeks of age. Neointima formation was evaluated by Elastica van Gieson staining 2 weeks after cuff placement. We assessed the following parameters in the femoral arteries prepared one week after cuff placement. Inflammatory cytokine and NADPH oxidase subunit were assessed by RT-PCR. Superoxide anion production, cell proliferation were evaluated by dihydroethidium staining, proliferating cell nuclear antigen (PCNA) staining respectively. p38 mitogen-activated protein kinase (p38MAPK) phosphorylation were evaluated by immunoblot analysis. Results: Birth weight was significantly lower in LP offspring (LPO) compared with NP offspring (NPO); however, LPO showed a similar body weight compared with NPO at 10 weeks of ages. Blood pressure at 12 weeks of age in LPO did not differ from NPO. Neointima formation was more exaggerated in LPO than NPO with enhanced oxidative stress and PCNA index in the injured artery. Expressions of MCP-1, IL-6, IL-1β and TNF-α in the femoral artery were more enhanced in LPO. Moreover, expressions of NADPH oxidase subunits, such as p22phox, p40phox, p47phox, p67phox, gp91phpx, Nox4 and Rac1 in the injured artery were enhanced in LPO than NPO. The phosphorylation level of p38MAPK was more increased in LPO than NPO. Conclusion: FGR led to the enhanced vascular remodeling via enhancement of stress responses such as inflammation and oxidative stress. These results suggest that FGR is a risk of vascular remodeling in the later life after birth.