[Malnutrition in early life and cardiovascular disease in adulthood].

Epidemiological and experimental studies have demonstrated that the risk of cardiovascular disease (CVD) in adulthood is influenced by the environment in early life. Intrauterine and early postnatal malnutrition and the following catch-up growth have a long-term effect on blood pressure and endothelial function in adulthood. Well-established prenatal or/and postnatal animal models are used to study the impact of different nutritional intervention on CVD in adulthood. This article reviews the early original cause of chronic CVD in adulthood with the hypothesis of DOHaD (the developmental origins of health and disease), and proposes possible preventions in early life on the basis of this theory.

Epigenetics of Notch1 regulation in pulmonary microvascular rarefaction following extrauterine growth restriction.

BACKGROUND: Extrauterine growth restriction (EUGR) plays an important role in the developmental origin of adult cardiovascular diseases. In an EUGR rat model, we reported an elevated pulmonary arterial pressure in adults and genome-wide epigenetic modifications in pulmonary vascular endothelial cells (PVECs). However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular consequences later in life remains unclear. METHODS: A rat model was used to investigate the physiological and structural effect of EUGR on early pulmonary vasculature by evaluating right ventricular systolic pressure and pulmonary vascular density in male rats. Epigenetic modifications of the Notch1 gene in PVECs were evaluated. RESULTS: EUGR decreased pulmonary vascular density with no significant impact on right ventricular systolic pressure at 3 weeks. Decreased transcription of Notch1 was observed both at 3 and 9 weeks, in association with decreased downstream target gene, Hes-1. Chromatin immunoprecipitation and bisulfite sequencing were performed to analyze the epigenetic modifications of the Notch1 gene promoter in PVECs. EUGR caused a significantly increased H3K27me3 in the proximal Notch1 gene promoter, and increased methylation of single CpG sites in the distal Notch1 gene promoter, both at 3 and 9 weeks. CONCLUSIONS: We conclude that EUGR results in decreased pulmonary vascular growth in association with decreased Notch1 in PVECs. This may be mediated by increased CpG methylation and H3K27me3 in the Notch1 gene promoter region.