Inhibition of T-cell activation attenuates hypertension, TNFα, IL-17, and blood-brain barrier permeability in pregnant rats with angiogenic imbalance.
PROBLEM
Angiogenic imbalance during pregnancy is associated with immune activation, hypertension, increased T cell infiltration, and neurological insults.


METHOD OF STUDY
On gestational day (GD) 12, timed-pregnant rats were infused with anti-angiogenic factors sFlt-1 and sEndoglin (4.7 and 7 μg/kg) to create HELLP syndrome via mini-osmotic pumps for 8 days, with a subset of these rats having Orencia (2 mg/kg) infused on GD13. On GD19, blood-brain barrier (BBB) permeability was evaluated via Evan's Blue infusion, blood was collected for T-cell measurements, inflammatory cytokine secretion. Brain tissues were also collected to examine inflammatory cytokine infiltration.


RESULTS
T-cell attenuation with Orencia decreased circulating CD4(+) and CD8(+) T cells, circulating tumor necrosis factor alpha (TNFα) and IL-17, BBB permeability and significantly decreased biochemical evidence of HELLP compared to untreated HELLP rats.


CONCLUSIONS
These data support the hypothesis that T cells have a critical role in contributing to the pathophysiology that is seen in angiogenic imbalance during pregnancy.
['Bean|Cynthia|C|', 'Spencer|Shauna-Kay|SK|', 'Bowles|Teylor|T|', 'Kyle|Patrick B|PB|', 'Williams|Jan M|JM|', 'Gibbens|Jacob|J|', 'Wallace|Kedra|K|']
D000069594:Abatacept D020533:Angiogenesis Inhibitors D000818:Animals D000893:Anti-Inflammatory Agents D001812:Blood-Brain Barrier D002199:Capillary Permeability D004195:Disease Models, Animal D000071063:Endoglin D005260:Female D017359:HELLP Syndrome D006801:Humans D006973:Hypertension D018836:Inflammation Mediators D020381:Interleukin-17 D008213:Lymphocyte Activation D009389:Neovascularization, Pathologic D011247:Pregnancy D051381:Rats D017207:Rats, Sprague-Dawley D013601:T-Lymphocytes D014409:Tumor Necrosis Factor-alpha D040281:Vascular Endothelial Growth Factor Receptor-1
blood-brain barrier HELLP syndrome CD4+ T cells TNFa hypertension, pregnancy brain