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

Abstract

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.

Vitamin D restores angiogenic balance and decreases tumor necrosis factor‐α in a rat model of pre‐eclampsia

“…Women with PE usually have abnormal immune balance favoring pro‐inflammatory factors, for example B cells, T cells, inflammatory cytokines as well as autoantibodies against angiotensin type I receptor, which could stimulate the generation of anti‐angiogenic protein‐soluble FMS‐like tyrosine kinase‐1 (sFlt‐1) . Reviews in the past decade emphasized the close relationship between altered placental vascular development and PE . Vascular endothelial growth factor (VEGF) is crucial in the vasculogenesis and angiogenesis involved in placental development .…”

Angiogenic Gene Expression in Down Syndrome Fetal Hearts

“…Abnormal angiogenesis has also been related to other obstetric and fetal conditions such as peripartum cardiomyopathy and fetal cardiac defects, opening up new challenges for our understanding of angiogenic involvement in maternal cardiovascular function and fetal cardiac development [25]. Reduced maternal serum PlGF at 11-13 weeks has been reported in pregnancies that subsequently develop preeclampsia and intrauterine growth restriction [26,][27] and in those with fetal trisomy 21 [28,29].…”

What Should Be Generalized Diagnostic Markers for Peripartum Cardiomyopathy?

“…1,5-7 For example, high maternal plasma sFlt1/PIGF values have been shown to be associated with preeclampsia and stillbirth and are thought be a risk factor for the development of PPCM. 7 However, Mebazaa et al demonstrate that in postpartum PPCM patients the sFlt1/PIGF ratio is rather lower, PIGF is higher and sFlt1 is similar compared with nonpregnant AHF patients. 3 Furthermore, postpartum PPCM patients have lower sFlt1/PIGF ratio and sFlt1 values and a similar PIGF value compared with healthy pregnant women; in addition their sFlt1/PIGF ratio and sFlt1 are lower and PIGF similar compared with healthy pregnant women at delivery (Table).…”

“…In addition, a splice variant of Flt-1, sFlt-1, is expressed in the placenta and has antiangiogenic effect by binding VEGF in the extracellular space. 7 Angiogenic imbalance such as overproduction of sFlt-1 is thought to initiate preeclampsia. Because preeclampsia sometimes predisposes to PPCM, sustained overproduction of sFlt-1 is thought to be a cause of PPCM.…”