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Principal Investigator: Babbette LaMarca
Organization: UNIVERSITY OF MISSISSIPPI MED CTR
Fiscal Year: 2024
Award: $501,050
Funding agency: National Heart Lung and Blood Institute
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?
Terms: <21+ years old><Address><Adoptive Transfer><Adult><Adult Children><Adult Daughters><Adult Human><Adult Offspring><Adult Sons><Affect><Allelism Test><Angiotensin AT1 Receptor><Angiotensin II Type 1 Receptor><Attenuated><Autoantibodies><Brain Vascular Disorders><COVID crisis><COVID epidemic><COVID infected patient><COVID pandemic><COVID patient><COVID positive patient><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infected patient><COVID-19 infection><COVID-19 pandemic><COVID-19 patient><COVID-19 period><COVID-19 positive patient><COVID-19 public health crisis><COVID-19 virus infection><COVID-19 years><COVID19 infection><COVID19 patient><COVID19 positive patient><CV-19><Cardiovascular Diseases><Cell Body><Cell Culture Techniques><Cell secretion><Cells><Cells Placenta-Tissue><Cellular Secretion><Cephalalgia><Cephalgia><Cephalodynia><Cerebrovascular Disease><Cerebrovascular Disorders><Cerebrum><Cessation of life><Chronic><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Common Rat Strains><Complementation Test><Coronavirus Infectious Disease 2019><Cranial Pain><Cytotoxic cell><Data><Death><Development><Differences between sexes><Differs between sexes><Disease><Disorder><Disturbance in cognition><Dysfunction><EPH Gestosis><Engineering><Exhibits><Female><Fetal Growth><Fetal Growth Restriction><Fetal Growth Retardation><Functional disorder><Genetic Complementation Test><Gestation><Head Pain><Headache><History><Hospitals><Hypertension><IUGR><Immune><Immune Cell Activation><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Impaired cognition><In Vitro><Incidence><Inflammation><Inflammatory><Intracranial Vascular Diseases><Intracranial Vascular Disorders><Intrauterine Growth Retardation><Ischemia><K lymphocyte><Kidney><Kidney Urinary System><Link><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Medical center><Memory Loss><Mississippi><Modeling><Molecular><NK Cell Activation><NK Cells><Natural Killer Cell Activation><Natural Killer Cells><Normal Placentoma><Pathogenesis><Pathway interactions><Patients><Peptides><Perfusion><Perinatal><Peripartum><Phenotype><Physiologic><Physiological><Physiopathology><Placenta><Placenta Embryonic Tissue><Placentome><Postpartum Hypertension><Postpartum Period><Pre-Eclampsia><Preeclampsia><Pregnancy><Pregnancy Toxemias><Pregnant Women><Production><Proteinuria-Edema-Hypertension Gestosis><Rat><Rats Mammals><Rattus><Receptor, Angiotensin, Type 1><Recording of previous events><Renal function><Research><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 infection history><SARS-CoV-2 pandemic><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV2 infection><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Sex Differences><Sexual differences><Techniques><Testing><Trans Test><Tumor Cell><Universities><Uterus><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Virus><Woman><adulthood><angiotensin II type I receptor><attenuate><attenuates><autoimmune antibody><autoreactive antibody><blood pressure elevation><brain vascular disease><brain vascular dysfunction><cardiovascular disorder><cell culture><cell cultures><cerebral><cerebral vascular disease><cerebral vascular dysfunction><cerebrovascular dysfunction><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><cognitive dysfunction><cognitive function><cognitive loss><complementation analysis><complementation approach><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease infected patient><coronavirus disease pandemic><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 patient><coronavirus infectious disease-19><coronavirus patient><developmental><elevated blood pressure><endothelial dysfunction><expectant mother><expecting mother><head ache><hemodynamics><high blood pressure><histories><history of COVID infection><history of COVID-19 infection><hyperpiesia><hyperpiesis><hypertensive><hypertensive disease><hypertensive disorder><immune activation><impaired fetal growth><in vivo><increase in blood pressure><increased blood pressure><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammation marker><inflammatory marker><intra-uterine growth><intra-uterine growth restriction><intra-uterine growth retardation><intracranial vascular dysfunction><intrauterine growth><intrauterine growth restriction><kidney function><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><male><maternal hypertension><maternal morbidity><memory decline><neoplastic cell><normotensive><novel><offspring><pathophysiology><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><perinatal morbidity><persistent COVID-19><pharmacologic><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><post-partum><pre-eclamptic><pregnancy toxemia/hypertension><pregnant><pregnant mothers><prenatal growth disorder><pressure><prolonged COVID-19 symptoms><renal><response><self reactive antibody><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social role><vascular constriction><vasoconstriction><womb>