17-Hydroxyprogesterone caproate lowers angiotensin II type 1 receptor agonistic autoantibody and improves hypertension in early-onset preeclampsia

Preeclampsia (PE), new onset hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation, affects 8% of all pregnancies in the U.S. and it is associated with progesterone deficiency, chronic inflammation, elevated angiotensin II type 1 receptor agonistic autoantibody (AT1-AA) and endothelial dysfunction. Currently, the early delivery of the feto-placental remains the best treatment for PE. Elevations in progesterone and T helper 2 cytokines favor the immunotolerance of the fetus during healthy pregnancy. Progesterone, through its receptors, stimulates anti-inflammatory and vasodilatory pathways. Therefore, this study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), lowers AT1-AA and inflammation while reducing maternal blood pressure in women with early-onset preeclampsia (EO-PE). PE women received 17-OHPC (250 mg, I.M.) and blood draws were collected before and after 17-OHPC treatment. Placentas were collected at the delivery. Progesterone and PIBF levels were 15.4 +/- 45.6 pg/mL (n=12), 14.4 +/- 1.0 ng/mL in PE (n=10), which significantly increased to 155+/-57.0 pg/mL, 16.39 +/-0.74 ng/mL (p< 0.05 vs. PE) in PE+17-OHPC (n=6). TNF-alpha and IL-6 were 41.3 +/- 3.9 pg/mL (n=8), 20.1 +/-7.9 (n=11) in PE, which decreased to 21.1+/-5.5 (n=6, p< 0.05 vs. PE), 5.2+/-2.1 in PE+17-OHPC (n=5). AT1-AA levels were 23+/-5.2 ΔBPM in PE (n=5), which significantly reduced to 2.1 ΔBPM in PE+17-OHPC (n=8, p< 0.05). 17-OHPC prolonged time of delivery beyond 72h on average and maternal blood pressure was 148 +/- 3.7 mmHg in PE (n=19), which significantly decreased to 136+/-4 in PE+17-OHPC (n=14, p< 0.05). In conclusion, 17-OHPC reduces AT1-AA and inflammation while improved blood pressure and maternal outcomes in response to early-onset preeclampsia. Supported by NIH grants RO1HD067541, 1U54GM115428, P20GM121334 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.