Fetoplacental Vascular Endothelial Dysfunction as an Early Phenomenon in the Programming of Human Adult Diseases in Subjects Born from Gestational Diabetes Mellitus or Obesity in Pregnancy

Figure 4

L-Arginine metabolism in hypercholesterolaemia. In human endothelial cells, L-arginine is taken up via cationic amino acid transporter 1 (hCAT-1) which is then metabolized by either the endothelial nitric oxide synthase (eNOS) into L-citrulline and nitric oxide (NO), or via arginases (ARG) into L-ornithine and urea, phenomena conforming a normal endothelial function phenotype. These mechanisms occur in a condition recognized as maternal physiological hypercholesterolaemia (MPH), which has been shown to be associated with early states of fetal vasculature atherosclerosis. However, in a state of maternal supraphysiological hypercholesterolaemia (MSPH) (see text), hCAT-1 and eNOS expression and activity are reduced (white down arrow) leading to reduced (segmented light-blue arrows) L-arginine uptake and NO synthesis, respectively. However, a higher (white up arrow) expression and activity of ARG (most likely arginase 2) leads to increased formation of L-ornithine and urea. The alterations seen in endothelial cells from pregnancies with MSPH result in endothelial dysfunction contributing in a larger proportion to fetal vasculature atherosclerosis compared with MPH. From data in [129, 130, 136, 138].