A 28-year-old primigravida at 32 weeks presents with BP 158/106 mmHg, proteinuria 2+ on dipstick, and severe headache. Platelet count is 78,000/µL, ALT 120 U/L, AST 110 U/L, and LDH 850 U/L. Which of the following best describes the mechanism by which sFlt-1 (soluble FMS-like tyrosine kinase-1) contributes to the endothelial dysfunction in this condition?
- A sFlt-1 activates VEGF receptors on endothelial cells, causing excessive vasodilation and capillary leak
- B sFlt-1 acts as a decoy receptor that sequesters free VEGF and PlGF, reducing angiogenic signaling and promoting endothelial injury ✓
- C sFlt-1 directly activates complement cascade leading to thrombotic microangiopathy
- D sFlt-1 inhibits thromboxane A2 synthesis, tipping the prostacyclin:thromboxane ratio toward vasoconstriction
Explanation
In pre-eclampsia, placental ischemia triggers excess release of sFlt-1, a truncated soluble form of the VEGF receptor (Flt-1/VEGFR-1). sFlt-1 acts as a circulating decoy receptor that sequesters free VEGF and placental growth factor (PlGF), preventing them from binding to endothelial VEGF receptors. This anti-angiogenic state impairs endothelial maintenance, leading to endothelial dysfunction, increased vascular permeability, hypertension, and proteinuria. The sFlt-1/PlGF ratio is now used clinically to predict pre-eclampsia. Options C and D describe separate pathways that are secondary; option A is the opposite of the mechanism.
Reference: Williams Obstetrics, 26th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.