Placental Microvasculature in Pregnancies Complicated by HIV

项目总结 HIV阳性妊娠的不同结局，如胎儿生长受限(FGR)，从病因上讲是不好的 可以理解，但归因于子宫胎盘功能不全。FGR是一种严重的不良后果 暴露于艾滋病毒的婴儿的相关持久发病率。迫切需要进一步的研究来更好地 了解胎盘的病理生理学，以便预测、诊断、监测和潜在地 防止FGR。我们先前的研究表明，生殖系统的微血管氧化应激增加 高龄女性艾滋病毒携带者(WLHIV)和暗示可能的胎盘病理生理学。臀部活组织检查 绝经前无明显心血管危险因素的WLHIV显示严重的内皮功能障碍和 还原的一氧化氮。这些在未怀孕的WLHIV中的发现可能是未来的早期标志 心血管发病率和可能的全身微血管功能障碍的问题，包括在 胎盘。尽管臀部组织的这些发现不能直接推断到胎盘 微血管系统，我们假设HIV感染或ART对 微血管病理生理学，同样影响胎盘，对胎儿有害 成长。关于人类胎盘微血管的有限文献，特别是关于胎盘生长的研究 限制，产生了相互矛盾的结果，这主要归因于方法上的不一致。 为了进一步探索这一假设，我们提议进行一项试验性研究，以复制臀肌使用的方法学。 以了解胎盘组织中微血管一氧化氮(NO)、反应性的差异 妊娠合并艾滋病毒和艾滋病患者的氧物种(ROS)、收缩能力和内皮功能障碍 生长限制。解决艾滋病毒相关的合并症和并发症，特别是 心血管疾病是NIH艾滋病研究办公室声明的优先事项，并更好地了解 与妊娠合并艾滋病毒相关的不良结局的潜在病理生理学 对WLHIV及其怀孕的至关重要的影响。具体地说，我们的目标是 确定测量心脏微血管收缩和内皮功能的最佳方法 人类胎盘，并采用以前用来测量胎盘的实验室方法 2)对微血管NO的差异进行定量评估， 妊娠合并HIV感染的12例胎盘的ROS、收缩功能和内皮功能障碍 无FGR和12个胎盘的HIV阴性的配对对照有和没有FGR。 这项先导性研究是更好地理解、诊断和管理 胎盘病理生理学与妊娠不良胎儿和新生儿结局的关系 因感染艾滋病毒而复杂化。

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.