Endocrine Abstracts

BACKGROUND Human and animal evidence indicates that poor maternal nutrition leads to programmed endothelial dysfunction and hypertension in offspring. In humans, endothelial dysfunction has been observed in independent cohorts studied aged 7 and 11, but explanatory molecular mechanisms are lacking. Endothelial function, and synthesis of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS), relies on nutrient supply of L-arginine, with maternal dietary restriction in rat pregnancies consistently leading to hypertension in adult offspring. This supply is dependent on human Cationic Aminoacid Transporter-1 (hCAT-1). HYPOTHESIS Endothelial function is programmed, with low birth weight associated with a permanent decreased expression of hCAT-1 and eNOS, detectable at birth. OBJECTIVE To use quantitative real time PCR, to assess expression of hCAT-1 and eNOS in human neonatal vascular endothelium, and correlate this with auxology. METHODS After ethical approval and informed written consent, nine umbilical cords were obtained from term elective caesarian sections, across a range of birth weights. Human Umbilical Vein Endothelial Cells (HUVECs) were extracted and cultured. RNA was extracted and DNAse treated prior to undertaking real time quantitative RT-PCR for hCAT-1 and eNOS. Data was normalised to expression of beta-actin. Measurements were taken of Birth Weight (BW), length, Occipito-Frontal Circumference (OFC) and Mid Upper Arm Circumference (MUAC). RESULTS There is a 16-fold variation in endothelial hCAT-1 expression between neonates. hCAT-1 expression was strongly correlated with OFC (r=0.805; p=0.004), BMI (r=0.863; p=0.001), BW (r=0.686; p=0.021) and MUAC (r=0.65; p=0.029). Simple linear regressions between hCAT-1 expression and each variate established a strong relationship with OFC: log_e (hCAT-1 expression) = 0.404 x OFC - 14.13 (F pr.=0.009; R²=0.593). CONCLUSIONS This is the first study to provide a molecular mechanism for the programming of human endothelial dysfunction. Whilst larger numbers are needed to confirm these findings, our data may have important implications for adult vascular health.