Update on the Pathophysiological Implications and Clinical Role of Angiogenic Factors in Pregnancy

Angiogenic markers are now being incorporated into clinical practice for the screening, diagnosing, and monitoring of preeclampsia. Pregnancy requires both vasculogenesis and angiogenesis in the fetal compartment and angiogenesis in the maternal compartment. Abnormal angiogenesis in the placenta determines impaired remodeling of the maternal spiral arteries and placental underperfusion that may ultimately lead to fetal growth restriction and maternal preeclampsia. The dysregulation of angiogenesis in the placenta and maternal-fetal circulation has emerged as one of the main pathophysiological features in the development of placental insufficiency and its clinical consequences. Abnormal angiogenesis has also been related to other obstetric and fetal conditions such as peripartum cardiomyopathy and fetal cardiac defects. This opens up new challenges for our understanding of angiogenic involvement in maternal cardiovascular function and fetal cardiac development, and it offers new clinical opportunities. This review summarizes the current knowledge of the pathophysiological implications and the clinical role of angiogenic factors in pregnancy.

Chronic prenatal hypoxia sensitizes β-adrenoceptors in the embryonic heart but causes postnatal desensitization

Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. β-Adrenoceptors (β-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardiac β-AR signaling and the incidence of alterations in the juvenile β-AR system due to the embryonic treatment. We measured functional β-AR density (Bmax) through binding with [3H]CGP-12177 and the effect of agonists on β-AR-dependent contractility (pEC50) through concentration-response curves to epinephrine. Eggs from broiler chickens were incubated in normoxia (N, 21% O2) or chronic hypoxia (H, 14% O2). Cardiac tissue from embryos and juveniles was used (15 and 19 day of embryonic development and 14 and 35 days posthatching, E19, E15, P14, and P35, respectively). Relative cardiac enlargement was found in the hypoxic groups at E15, E19, and P14, but not P35. Bmax significantly decreased in E19H. Bmax more than doubled posthatching but decreased from P14 to P35. The sensitivity to epinephrine was lower in E19N compared with E15N, but hypoxia increased the sensitivity to agonist in both E15H and E19H. Despite maintained receptor density, the P35H juvenile displayed a decreased sensitivity to β-AR agonist, something that was not seen in P14H. The postnatal decrease in β-AR sensitivity as an effect of chronic prenatal hypoxia, without a concomitant change in β-AR density, leads us to conclude that the embryonic hypoxic challenge alters the future progression of β-AR signaling and may have important implications for cardiovascular function in the adult.