Publicación: PREECLAMPSIA AND INCREASED PERMEABILITY OVER THE BLOOD-BRAIN BARRIER: A ROLE OF VASCULAR ENDOTHELIAL GROWTH RECEPTOR 2
Fecha
2021
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AMERICAN JOURNAL OF HYPERTENSION
Resumen
BACKGROUND: CEREBRAL COMPLICATIONS IN PREECLAMPSIA ARE LEADING CAUSES OF MATERNAL MORTALITY WORLDWIDE BUT PATHOPHYSIOLOGY IS LARGELY UNKNOWN AND A CHALLENGE TO STUDY. USING AN IN VITRO MODEL OF THE HUMAN BLOOD-BRAIN BARRIER (BBB), WE EXPLORED THE ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2 (VEGFR2) IN PREECLAMPSIA.
METHODS: THE HUMAN BRAIN ENDOTHELIAL CELL LINE (HCMEC/D3) CULTURED ON TRANWELLS INSERT WAS EXPOSED (12 HOURS) TO PLASMA FROM WOMEN WITH PREECLAMPSIA (N = 28), NORMAL PREGNANCY (N = 28), AND NONPREGNANT (N = 16) CONTROLS. TRANSENDOTHELIAL ELECTRICAL RESISTANCE (TEER) AND PERMEABILITY TO 70 KDA FLUORESCEIN ISOTHIOCYANATE (FITC)-DEXTRAN WERE MEASURED FOR THE ASSESSMENT OF BBB INTEGRITY. WE EXPLORED POSSIBLE UNDERLYING MECHANISMS, WITH A FOCUS ON THE EXPRESSION OF TIGHT JUNCTION PROTEINS AND PHOSPHORYLATION OF 2 TYROSINE RESIDUES OF VEGFR2, ASSOCIATED WITH VASCULAR PERMEABILITY AND MIGRATION (PY951) AND CELL PROLIFERATION (PY1175). PLASMA CONCENTRATIONS OF SOLUBLE FMS-LIKE TYROSINE KINASE-1 (SFLT-1) AND PLACENTAL GROWTH FACTOR (PLGF) WERE ALSO MEASURED.
RESULTS: HCMEC/D3 EXPOSED TO PLASMA FROM WOMEN WITH PREECLAMPSIA EXHIBITED REDUCED TEER AND INCREASED PERMEABILITY TO 70 KDA FITC-DEXTRAN. THESE CELLS UPREGULATED THE MESSENGER RIBONUCLEIC ACID (MRNA) LEVELS OF VEGFR2, AND PY951-VEGFR2, BUT REDUCED PY1175-VEGFR2 (P < 0.05 IN ALL CASES). NO DIFFERENCE IN MRNA EXPRESSION OF TIGHT JUNCTION PROTEIN WAS OBSERVED BETWEEN GROUPS. THERE WAS NO CORRELATION BETWEEN ANGIOGENIC BIOMARKERS AND BBB PERMEABILITY.
CONCLUSIONS: WE PRESENT A PROMISING IN VITRO MODEL OF THE BBB IN PREECLAMPSIA. SELECTIVE TYROSINE PHOSPHORYLATION OF VEGFR2 MAY PARTICIPATE IN THE INCREASED BBB PERMEABILITY IN PREECLAMPSIA IRRESPECTIVE OF PLASMA CONCENTRATIONS OF ANGIOGENIC BIOMARKERS.
