Placental Microvasculature in Pregnancies Complicated by HIV

妊娠期 HIV 并发的胎盘微血管

• 批准号: 10227665
• 负责人: Rachel K Scott
• 金额: $ 23.51万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227665
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Age; Biological Markers; Biopsy; Blood Vessels; Cardiovascular system; Conflict (Psychology); Data; Diagnosis; Endothelium; Etiology; Fetal Growth; Fetal Growth Retardation; Follow-Up Studies; Functional disorder; Future; Growth; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV antiretroviral; Harvest; Histology; Hospitals; Human; Infant; Joints; Laboratories; Literature; Measures; Methodology; Methods; Microvascular Dysfunction; Monitor; Morbidity - disease rate; Multicenter Studies; NIH Office of AIDS Research; Neonatal; Nitric Oxide; Outcome; Oxidative Stress; Pilot Projects; Placenta; Plasma; Population; Pregnancy; Premenopause; Prevalence; Protocols documentation; Quantitative Evaluations; Reactive Oxygen Species; Research; Research Personnel; Severities; Skin; Time; Tissues; Ultrasonography; Universities; University Hospitals; Washington; Woman; adverse outcome; antiretroviral therapy; cardiovascular risk factor; clinical care; comorbidity; endothelial dysfunction; experience; fetal; interest; laboratory equipment; laboratory facility; molecular marker; neonatal outcome; prevent; recruit; reproductive; skills

PROJECT SUMMARY Disparate outcomes in HIV positive pregnancies, such as fetal growth restriction (FGR), are etiologically poorly understood, but are attributed to uteroplacental insufficiency. FGR is a serious adverse outcome with associated lasting morbidity for the HIV exposed infant. Further research is desperately needed to better understand the placental pathophysiology in order to predict, diagnose, monitor, and potentially prevent FGR. Our previous research demonstrated increased microvascular oxidative stress in reproductive age women living with HIV (WLHIV) and alludes to a possible placental pathophysiology. Gluteal biopsies in premenopausal WLHIV without overt cardiovascular risk factors revealed severe endothelial dysfunction and reduced nitric oxide. These finding in non-pregnant WLHIV may represent early markers of future cardiovascular morbidity and beg the question of possible systemic microvascular dysfunction, including in the placenta. Although these findings in gluteal tissue cannot be directly extrapolated to placental microvasculature, we hypothesize that there is of potential systemic effect of HIV infection or ART on microvascular pathophysiology, similarly affecting the placenta, with a detrimental effect on fetal growth. The limited literature on human placental microvessels, particularly studies of placentas with growth restriction, yielded conflicting results largely attributable to methodological inconsistencies. To further explore this hypothesis, we are proposing a pilot study to replicate the methodology used in gluteal tissue in placental tissue and to characterize differences in placental microvascular nitric oxide (NO), reactive oxygen species (ROS), contractility, and endothelial dysfunction in pregnancies complicated by HIV and growth restriction. Addressing HIV-associated comorbidities and complications, specifically cardiovascular, are stated priorities of the NIH Office of AIDS Research and better understanding the underlying pathophysiology of the adverse outcomes related to pregnancies complicated by HIV have critically important implications for WLHIV and their pregnancies. Specifically our aims are 1) To determine the best methods of measuring contractility and endothelial function of microvessels in the human placenta and to adapt laboratory methodologies previously employed to measure the same parameters in gluteal tissue; 2) To undertake a quantitative evaluation of differences in microvascular NO, ROS, contractility, and endothelial dysfunction in 12 placentas of pregnancies complicated by HIV with and without FGR and 12 placentas of pregnancies in HIV-negative matched controls with and without FGR. This pilot research is the crucial next step to better understanding, diagnosing and managing the placental pathophysiology associated with adverse fetal and neonatal outcomes in pregnancies complicated by HIV.

项目总结