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 2

Endothelial L-arginine/NO signalling pathway in gestational diabetes mellitus and obesity in pregnancy. In human endothelial cells L-arginine is taken up via cationic amino acid transporters 1 (hCAT-1) accumulating this amino acid in the intracellular space. L-Arginine is then metabolized by the endothelial nitric oxide synthase (eNOS) into L-citrulline and nitric oxide (NO) as a co-product. Gestational diabetes mellitus is associated with higher expression and activity of hCAT-1 leading to supraphysiological accumulation of L-arginine. This phenomenon results in higher L-arginine metabolism by eNOS due to increased expression and activity of this enzyme leading to overproduction of NO. In endothelial cells from OP there is no information addressing whether this pathological condition alters L-arginine transport and intracellular accumulation, but reduces eNOS expression and activity leading to lower than physiological synthesis of NO.