Elevated BNP expression in mouse offspring left ventricles after protein restriction in utero

Abstract

Objectives: We have previously shown that cyclin G1expression is reduced in fetal hearts after in utero protein restriction (PR) suggesting reduced cardiac cell cycle. However no difference in cyclin G1 expression was seen in adult offspring hearts. We hypothesised that the hearts of adult PR group should be under greater stress to maintain cardiac output. We therefore measured brain natriuretic peptide (BNP) expression in fetal hearts and left ventricles of adult offspring in the control (C) and PR groups because BNP is a marker of left ventricular dysfunction during volume overload or cardiac fibrosis (Nishikimi et al. Cardiovasc Res. 2006).Methods and results: Pregnant CD1 mice were placed on C (18% casein) or PR (9% casein) diet. Fetal hearts were collected on day 12 of gestation (C, n =11, PR, n =10) and the left ventricles (LV) of adult offspring at 6 months (C,n =17, PR, n =17). Fetal heart BNP mRNA expression relative to unit total RNA as measured by real-time PCR was similar in C and PR (C, 0.858F0.104 vs. PR, 0.761F0.096, p =NS). However, BNP expression in adult LV was greater in the PR than C (C, 7.043F0.68 vs. PR, 11.012F1.54, p =0.04).Conclusion: These results indicate that protein restriction in pregnancy induces cellular changes (indicated by cyclin G1 changes) in the fetal heart which places it under stress in adulthood (elevated BNP production). Because BNP can suppress ventricular remodelling, we are presently investigating cardiac structural changes to assess whether these alterations are adaptive or maladaptive