Soluble FMS-like tyrosine kinase 1 (SFLT1) is a protein that regulates the body’s vascular system. As a circulating molecule, it plays a fundamental role in controlling angiogenesis, the formation of new blood vessels. SFLT1 acts as an antagonist, essentially putting a brake on the growth-promoting signals that drive vascular development. Maintaining stable SFLT1 levels is important for systemic vascular health.
The Molecular Identity and Primary Targets
SFLT1 is a soluble, truncated form of a larger, membrane-bound receptor protein called FMS-like tyrosine kinase 1 (FLT1), also known as Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1). This soluble protein is produced through an alternative splicing mechanism of the FLT1 gene. The resulting molecule contains the receptor’s extracellular binding domains but lacks the anchoring and signaling components. Because of this structure, SFLT1 is released into the bloodstream, circulating freely.
Functionally, SFLT1 acts as a “decoy receptor” by binding to its target molecules before they can activate full-length receptors on endothelial cells. SFLT1’s primary targets are two pro-angiogenic factors: Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PlGF). By binding to these factors, SFLT1 neutralizes their activity, preventing them from stimulating blood vessel growth and maintaining the health of the vessel lining.
Regulating Healthy Blood Vessel Growth
The core function of SFLT1 in a healthy body is to act as a negative regulator, ensuring that angiogenesis remains balanced and controlled. While new blood vessels are necessary for growth and repair, their formation must be moderated to prevent excessive or disorganized vascularization. SFLT1 provides this counter-signal, maintaining vascular homeostasis across various tissues, including the kidneys, brain, and liver.
A balance between SFLT1 and its ligands (free VEGF and PlGF) is necessary to sustain the health of the endothelial cells lining the blood vessels. These pro-angiogenic factors maintain the integrity and function of the microvasculature. In a normal pregnancy, the placenta releases a moderate amount of SFLT1 to manage the increasing levels of VEGF and PlGF, regulating the maternal blood supply without causing systemic dysfunction.
The Role in Preeclampsia and Pregnancy Complications
The balance of angiogenic factors is severely disrupted in Preeclampsia, a hypertensive disorder of pregnancy. In this condition, the placenta produces and releases excessive SFLT1 into the maternal circulation. This excessive secretion is often triggered by placental hypoperfusion, a state where the placenta is not receiving adequate blood flow, which can lead to localized hypoxia.
The high SFLT1 level acts like a sponge, scavenging nearly all circulating free VEGF and PlGF. This depletion of pro-angiogenic factors is central to the disease’s mechanism, causing widespread damage to the maternal endothelial cells (the lining of blood vessels). This systemic endothelial dysfunction leads to the clinical signs of Preeclampsia, including elevated blood pressure (hypertension) and protein leakage into the urine (proteinuria).
The damage extends to organs like the kidneys, where the lack of VEGF disrupts the specialized cells maintaining the filtration barrier, resulting in proteinuria. The reduction in pro-angiogenic signaling also causes blood vessels to constrict, contributing directly to the hypertensive state. Elevated SFLT1 concentrations can sometimes be detected in maternal serum up to five weeks before clinical symptoms appear.
How SFLT1 Levels Are Used Clinically
The imbalance between SFLT1 and PlGF is used clinically as a diagnostic and prognostic tool for Preeclampsia. Medical professionals measure the SFLT1 to PlGF ratio, which provides a numerical value reflecting the angiogenic balance in the maternal circulation. This ratio is considered a more accurate predictor than measuring either protein alone, as it captures the net effect of the anti-angiogenic and pro-angiogenic factors.
The SFLT1/PlGF ratio is useful for managing pregnant women with suspected Preeclampsia, typically in the second and third trimesters. Specific cut-off values, established through large-scale studies like the PROGNOSIS trial, guide clinical decision-making. A ratio of \(\leq 38\) is effective at ruling out the short-term development of Preeclampsia, often preventing unnecessary hospitalizations.
Conversely, an elevated ratio indicates a high risk of developing the condition or having an imminent diagnosis. For example, a ratio greater than 85 before 34 weeks of gestation, or greater than 110 after 34 weeks, suggests a high probability of Preeclampsia or related placental disorders. Monitoring this ratio helps physicians differentiate Preeclampsia from other hypertensive disorders, allowing for timely and targeted management to improve outcomes.