Overexpression of CD39 protects in a mouse model of preeclampsia

CD39 (NTPDase1), a critical immune and vascular ecto‐nucleotidase, hydrolyses pro‐inflammatory and pro‐thrombotic nucleotides (adenosine‐5′‐triphosphate (ATP) and adenosine diphosphate) to adenosine. In humans, CD39 is the dominant ecto‐nucleotidase in placental trophoblastic tissues and modulates ATP‐dependent trophoblastic functions. CD39 is an integral component of regulatory T cells (Treg), which are central to immunological tolerance and maintenance of normal pregnancy. We examined the impact of CD39 overexpression in a mouse model of preeclampsia. Matings were performed between virginal BALB/c female (wild‐type (WT) or CD39 transgenic (CD39TG)) and C57BL/6 male mice. On days 10 and 12 of pregnancy BALB/c Th1‐polarized cells were injected. Systolic blood pressure (SBP) was measured throughout pregnancy. Mice were sacrificed at day 15 of pregnancy. Following transfer of Th1‐polarized cells, SBP of pregnant WT mice increased (118 ± 3 mmHg to 142 ± 5 mmHg). Although ultrastructural changes were evident in the kidney this was not accompanied by significant proteinuria. SBP remained unchanged (115 ± 2 mmHg to 114 ± 3 mmHg) in pregnant CD39TG mice without evidence of renal lesions. We conclude that gestational hypertension can be induced in mice following transfer of maternally derived Th1‐polarized cells and that overexpression of CD39 is protective in this model.

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