ArticleAmerican journal of respiratory and critical care medicine2016
Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04918706 (An Explorative Study for Halting Inflammation in Patients With Emphysema by Administration of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells.), which is not on this map. Cited by 55 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.
An Explorative Study for Halting Inflammation in Patients With Emphysema by Administration of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells.
Who cites it
55 citing papers in PubMed, 96 citations in OpenAlex.
- BMP9 Modulates IL-33 Signaling to Mitigate EndMT in Pulmonary Arterial Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Sotatercept in Pulmonary Arterial Hypertension: Molecular Mechanisms, Clinical Evidence, and Emerging Role in Reverse Remodelling.International journal of molecular sciences · 2026Review
- Targeting Inflammation-Oxidative Stress Crosstalk: Advances and Challenges in Nanocarrier-Based Interventional Strategies for Pulmonary Arterial Hypertension.International journal of nanomedicine · 2026Review
- Retinal Assessment and the Retina-Choroid Link in Precapillary Pulmonary Hypertension: A Single-Center Cross-Sectional Study.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Endothelial Heterogeneity in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Mapping disease-specific vascular cell populations responsible for obliterative arterial remodelling during the development of pulmonary arterial hypertension.Cardiovascular research · 2025Article
- Article
- Pressure Points: Endothelial Responses to Shear Stress and Pressure in Health and Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2025Article
- The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview.Cells · 2025Review
- Topical frankincense treatment on relieving high-risk diabetic foot in rats by reducing inflammation and improving microcirculation.Frontiers in pharmacology · 2025Article
- Shear stress unveils patient-specific transcriptional signatures in PAH: Towards personalized molecular diagnostics.Theranostics · 2025Article
- Review
- Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.American journal of respiratory cell and molecular biology · 2024Article
- Defective CFTR modulates mechanosensitive channels TRPV4 and PIEZO1 and drives endothelial barrier failure.iScience · 2024Article
- Assessing causal associations of blood counts and biochemical indicators with pulmonary arterial hypertension: a Mendelian randomization study and results from national health and nutrition examination survey 2003-2018.Frontiers in endocrinology · 2024Observational
- Pentastatin, a matrikine of the collagen IVα5, is a novel endogenous mediator of pulmonary endothelial dysfunction.American journal of physiology. Cell physiology · 2023Article
- Article
- You Can't Spell Shear without "She": Mechanobiology and Sex Differences in Hypoxic Lung Disease.American journal of respiratory cell and molecular biology · 2023Article
- Pathophysiology and new advances in pulmonary hypertension.BMJ medicine · 2023Review
- CD39 in the development and progression of pulmonary arterial hypertension.Purinergic signalling · 2022Review
Corrections and comments
- Commented on by
Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
rationaleAltered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear.
objectivesWe hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo.
methodsPAH MVEC (n = 7) and PAH PAEC (n = 3) morphology, function, protein, and gene expressions were compared with control MVEC (n = 8) under static culture conditions and after 24, 72, and 120 hours of HSS. MEASUREMENTS AND MAIN
resultsPAH MVEC showed a significantly delayed morphological shear adaptation (P = 0.03) and evidence of cell injury at sites of nonuniform shear profiles that are critical loci for vascular remodeling in PAH. In clear contrast, PAEC isolated from the same PAH lungs showed no impairments. PAH MVEC gene expression and transcriptional shear activation were not altered but showed significant decreased protein levels (P = 0.02) and disturbed interendothelial localization of the shear sensor platelet endothelial cell adhesion molecule-1 (PECAM-1). The decreased PECAM-1 levels were caused by caspase-mediated cytoplasmic cleavage but not increased cell apoptosis. Caspase blockade stabilized PECAM-1 levels, restored endothelial shear responsiveness in vitro, and attenuated occlusive vascular remodeling in chronically hypoxic Sugen5416-treated rats modeling severe PAH.
conclusionsDelayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.
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.