Sex differences in hypertension, cognitive function and renal hemodynamics; a role for B cells and autoantibodies - Preeclampsia (PE) a disease estimated to affect 12% of deliveries at University of Mississippi Medical Center. The incidence of PE deliveries increased significantly at our hospital due to the COVID-19 pandemic. The rate of PE at UMMC rose from 12% to 28% in December of 2020 and was up to 42 % in April of 2021. PE is characterized by placental ischemia, inflammation, endothelial dysfunction, vasoconstriction, hypertension (HTN), IUGR and developmental origins of HTN in the offspring. We have shown that agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) stimulate to cause placental and cerebral dysfunction contributing to HTN in pregnant rats which is attenuated by blockade of the AT1-AA with the peptide ‘n7AAc’. One important unanswered question in PE research is the relative importance of B cells secreting AT1-AA to cause HTN and cerebral dysfunction in the pregnant mom or to cause adult HTN in her offspring. A second important unanswered question is does the sex of the baby correlate with immune cell (B cell) activation, level of AT1-AA and HTN during pregnancy or in adult offspring. Moreover, we don’t know the role of B cells to secrete the AT1-AA as mechanisms of a PE phenotype in pregnant patients with a history (Hx) of COVID 19 infection. Our preliminary data supporting AIM 1 are that AT1-AA are elevated in response to PE and in Normal pregnant adoptive transfer recipients of PE B cells. In addition, we show that postpartum (PP) AT1-AA induced hypertensive pregnant rats exhibit cerebrovascular dysfunction 4 months PP. Preliminary data supporting AIM 2 is that adoptive transfer of PE B cells cause HTN and AT1-AA in pregnant athymic nude recipient rats. Preliminary data supporting AIM 3 is that AT1-AA is produced in pregnant women with HTN and a history (Hx) of COVID during pregnancy and that adoptive transfer of B cells from PE women with a COVID 19 Hx during pregnancy increases blood pressure and AT1-AA in pregnant nude athymic recipient rats compared to B cells from normotensive women with a Hx of COVID during pregnancy. Based on our findings, we hypothesize that PE stimulated B cells secreting AT1- AA cause cerebral dysfunction and HTN during pregnancy and programming of HTN in adult male and female offspring which could be attenuated by AT1-AA blockade. Moreover, we hypothesize that a COVID 19 Hx during pregnancy results in AT1-AA that causes a PE phenotype during pregnancy which could be attenuated with AT1- AA blockade. Specific Aim 1. To test the hypothesis that perinatal AT1-AA results HTN, cerebrovascular dysfunction and cognitive decline in the dam and in adult male or female offspring. Specific Aim 2. To test the hypothesis that B2 cells secreting AT1-AA from PE women cause cerebral dysfunction and HTN during pregnancy and in adult male and female offspring. Does sex of the baby influence the activation of the placental B2 cells and levels of AT1-AA from PE women? Specific Aim 3. To test the hypothesis that B2 cells from PE+COVID-19 Hx patients cause AT1AA, cerebral dysfunction, IUGR, and HTN recipient pregnant rats. Does sex of the baby influence the activation of the placental B2 cells and levels of AT1-AA from PE women?
