期刊
CLINICAL CARDIOLOGY
卷 41, 期 2, 页码 220-227出版社
WILEY
DOI: 10.1002/clc.22892
关键词
Decidual Natural Killer Cells; Extravillous Trophoblast Cells; Hypoxia; Incomplete Materno-Fetal Immune Tolerance; Preeclampsia
资金
- Romanian-American Fulbright Commission
- National Heart, Lung, and Blood Institute (NHLBI): Cardiovascular Cell Therapy Network (CCTRN) [UM1 HL087318]
- University of Florida Regional Clinical Center CCTRN Training Core Supplement [UM1 HL087366]
- US Department of Defense: Women's Ischemia Treatment Reduces Events in Non-Obstructive CAD
- NHLBI: Brain-Gut Microbiome-Immune Axis in Hypertension [HL132448]
- Gatorade Trust through the University of Florida, Department of Medicine
- National Institutes of Health, National Center for Advancing Translational Sciences-University of Florida Clinical and Translational Science [UL1TR001427]
- PCORnet-OneFlorida Clinical Research Consortium, Clinical Data Research Network [1501-26692]
Pregnancy-related hypertension (PHTN) syndromes are a frequent and potentially deadly complication of pregnancy, while also negatively impacting the lifelong health of the mother and child. PHTN appears in women likely to develop hypertension later in life, with the stress of pregnancy unmasking a subclinical hypertensive phenotype. However, distinguishing between PHTN and chronic hypertension is essential for optimal management. Preeclampsia (PE) is linked to potentially severe outcomes and lacks effective treatments due to poorly understood mechanisms. Inadequate remodeling of spiral uterine arteries (SUAs), the cornerstone of PE pathophysiology, leads to hypoperfusion of the developing placenta. In normal pregnancies, extravillous trophoblast (EVT) cells assume an invasive phenotype and invade SUAs, transforming them into large conduits. Decidual natural killer cells play an essential role, mediating materno-fetal immune tolerance, inducing early SUA remodeling and regulating EVT invasiveness. Notch signaling is important in EVT phenotypic switch and is dysregulated in PE. The hypoxic placenta releases antiangiogenic and proinflammatory factors that converge upon maternal endothelium, inducing endothelial dysfunction, hypertension, and organ damage. Hypoxia-inducible factor 1- is upstream of such molecules, whereas endothelin-1 is a major effector. We also describe important genetic links and evidence of incomplete materno-fetal immune tolerance, with PE patients presenting with autoantibodies, lower T-reg, and higher T(h)17 cells. Thus, PE manifestations arise as a consequence of mal-placentation or/and because of a predisposition of the maternal vascular bed to excessively react to pathogenic molecules. From this pathophysiological basis, we provide current and propose future therapeutic directions for PE.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据