(720.6) Aspirin Treatment Improves Excess Activin A Associated Cardiac Dysfunction In Pregnancy

Poster Board Number: E148

Bhavisha Bakrania (University of Mississippi Medical Centre), Ana Palei (University of Mississippi Medical Centre, University of Mississippi Medical Centre), Sajid Shahul (University of Chicago), Michael Hall (University of Mississippi Medical Centre, University of Mississippi Medical Centre), Joey Granger (University of Mississippi Medical Centre)

Preeclampsia (PE) is a hypertensive disorder prevalent in 3-8% of pregnancies. The placenta plays a central role in PE as it releases anti-angiogenic, pro-inflammatory and pro-fibrotic factors into the maternal circulation to cause endothelial dysfunction and end organ damage, including cardiac dysfunction. PE women have elevated plasma levels of the pro-fibrotic factor, Activin A, that is associated with decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function and fibrosis. In a retrospective study, we recently showed that PE women administered aspirin had significantly reduced Activin A and improved GLS. Whether aspirin has a direct effect in improving cardiac function and reducing Activin A is not known. We hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction, and that aspirin treatment in late pregnancy improves GLS. To address this, Vehicle and Activin A treated (6 µg/day) rats were assigned to placebo or aspirin treatment (1 mg/day) groups (n = 8-12/group) on gestational day (GD) 14. All animals had an indwelling carotid catheter placed on GD 18, followed by a comprehensive echocardiography assessment and blood pressure measurement on GD19. Activin A infusion resulted in significant increases in circulating Activin A in the placebo group (Vehicle+Placebo, 701±45 pg/mL; Act+Placebo, 1248±121 pg/m; Plt;0.01). Interestingly, aspirin treatment reduced circulating Activin A, despite continual infusion (Act+Aspirin, 896±99 pg/mL, Plt;0.01), suggesting aspirin may degrade Activin A. Activin A infusion was associated with significantly impaired GLS (Vehicle+Placebo, -22.3±3.02 %; Activin+Placebo, -15.5±1.92 %; Plt;0.01) that was significantly improved with aspirin treatment (Activin+Aspirin, -19.2±1.47 %, Plt;0.01). Mean arterial pressure was not significantly different between groups, suggesting that Activin A associated cardiac dysfunction occurs independently of increases in blood pressure. These findings suggest that Activin A may induce cardiac abnormalities in women with PE, and that aspirin may be a potential treatment option.

This research was supported by the American Heart Association (18POST33990293) and the National Institutes of Health (R01HL1148191,lt;bgt;lt;igt; lt;/igt;lt;/bgt;P01HL051971, P20GM104357).