ArticleAmerican journal of physiology. Heart and circulatory physiology2013
The loss of sustained Ca(2+) signaling underlies suppressed endothelial nitric oxide production in preeclamptic pregnancies: implications for new therapy.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Reactive oxygen species in fetal growth restriction mechanisms and therapeutic directions (Review).International journal of molecular medicine · 2026Review
- An appraisal of the role of asymmetric dimethylarginine on endothelial impairment in preeclampsia comorbid with HIV infection.Frontiers in medicine · 2026Review
- Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.Comprehensive Physiology · 2024Review
- Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.Lab on a chip · 2024Article
- Src kinase partially mediates cytokine-induced endothelial dysfunction.Pregnancy hypertension · 2023Article
- Maternal-derived galectin-1 shapes the placenta niche through Sda terminal glycosylation: Implication for preeclampsia.PNAS nexus · 2023Article
- Mononuclear Cells Negatively Regulate Endothelial CaReproductive sciences (Thousand Oaks, Calif.) · 2023Article
- The role of immune cells and mediators in preeclampsia.Nature reviews. Nephrology · 2023Review
- Cytokine concentrations direct endothelial function in pregnancy and preeclampsia.The Journal of endocrinology · 2021Article
- Role of ROS/RNS in Preeclampsia: Are Connexins the Missing Piece?International journal of molecular sciences · 2020Review
- G Protein α Subunit 14 Mediates Fibroblast Growth Factor 2-Induced Cellular Responses in Human Endothelial Cells.Journal of cellular physiology · 2019Article
- Gasotransmitters in pregnancy: from conception to uterine involution.Biology of reproduction · 2019Review
- Pathophysiology of Cerebral Vascular Dysfunction in Pregnancy-Induced Hypertension.Current hypertension reports · 2019Review
- TNF-alpha inhibits pregnancy-adapted CaMolecular and cellular endocrinology · 2019Article
- Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal.Journal of cardiovascular development and disease · 2018Review
- Pregnancy-adapted uterine artery endothelial cell Ca2+ signaling and its relationship with membrane potential.Physiological reports · 2017Article
- Preeclampsia Downregulates MicroRNAs in Fetal Endothelial Cells: Roles of miR-29a/c-3p in Endothelial Function.The Journal of clinical endocrinology and metabolism · 2017Article
- Positive versus negative effects of VEGF165 on Ca2+ signaling and NO production in human endothelial cells.American journal of physiology. Heart and circulatory physiology · 2017Article
- Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia.The Journal of endocrinology · 2017Review
- Changes in Ca2+ Signaling and Nitric Oxide Output by Human Umbilical Vein Endothelium in Diabetic and Gestational Diabetic Pregnancies.Biology of reproduction · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Approximately 8% of pregnancies are complicated by preeclampsia (PE), a hypertensive condition characterized by widespread endothelial dysfunction. Reduced nitric oxide (NO) output in PE subjects has been inferred but not directly measured, and there is little understanding of why this occurs. To address this we have used direct imaging of changes in intracellular Ca(2+) concentration ([Ca(2+)]i) and NO in umbilical vein endothelium of normal and PE subjects that is still intact and on the vessel luminal surface. This was achieved by dissection and preloading with fura 2 and DAF-2 imaging dyes, respectively, before subsequent challenge with ATP (100 μM, 30 min). As a control to reveal the content of active endothelial nitric oxide synthase (eNOS) per vessel segment, results were compared with a maximal stimulus with ionomycin (5 μM, 30 min). We show for the first time that normal umbilical vein endothelial cells respond to ATP with sustained bursting that parallels sustained NO output. Furthermore, in subjects with PE, a failure of sustained [Ca(2+)]i bursting occurs in response to ATP and is associated with blunted NO output. In contrast, NO responses to maximal [Ca(2+)]i elevation using ionomycin and the levels of eNOS protein are more similar between groups than the responses to ATP. When the endothelial cells from PE subjects are isolated and allowed to recover in culture, they regain the ability under fura 2 imaging to show multiple [Ca(2+)]i bursts otherwise seen in the cells from normal subjects. Thus novel clinical therapy aimed at restoring function in vivo may be possible.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.