title: Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease.
abstract: Low birthweight is associated with increased rates of coronary heart disease, stroke, hypertension and non-insulin-dependent diabetes during adult life. This is thought to be the consequence of a 'programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may, hence, result from adaptations to a condition where placental nutrient supply fails to match fetal demand. Recently, compensatory feto-placental up-regulation of the nitric oxide system during fetal growth restriction (FGR) was shown. Particularly, restricted hypoxic fetuses present an elevation of nitrites and a reduction of asymmetric dimethylarginine. S-nitrosohemoglobin is consumed under hypoxic conditions. These events are followed by nitric oxide pathway down-regulation postnatally, increasing susceptibility to cardiovascular disorders later in life. The relative hyperoxia would favor any such occurrence through depletion of tetrahydrobiopterin secondary to oxygen radical formation. This concept may lead to new therapeutic strategies, based on tetrahydrobiopterin supplementation, free-radical scavenging, L-arginine administration and/or inhaled NO therapy in FGR hypoxic newborns, to improve their postnatal adaptation and to reduce the risk of metabolic pathologies in adult age.
authors: Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, 56100, Pisa, Italy.
authors: Silvia
authors: S
authors: Pisaneschi
authors: Antonio
authors: A
authors: Boldrini
authors: Andrea Riccardo
authors: AR
authors: Genazzani
authors: Flavio
authors: F
authors: Coceani
authors: Tommaso
authors: T
authors: Simoncini
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology*; D003920:Diabetes Mellitus / Q000209:etiology; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000503:physiopathology; D006801:Humans; D007230:Infant, Low Birth Weight / Q000502:physiology; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000096:biosynthesis; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015854:Up-Regulation / Q000502:physiology
chemical_list: D009569:Nitric Oxide