ArticleCirculation research2014
Genetic deletion of toll-like receptor 4 on platelets attenuates experimental pulmonary hypertension.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 63 citations in OpenAlex.
- The Gut Microbiome in Heart Failure: Pathways to Inflammation and Therapeutic Targets.Metabolites · 2026Review
- Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome.Frontiers in immunology · 2026Article
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- A Novel Role for Platelet-Endothelial Crosstalk in Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- From theory to platelets: unraveling the history and complexities of biased signaling.Blood vessels, thrombosis & hemostasis · 2025Review
- Nbeal2 knockout mice are not protected against hypoxia-induced pulmonary vascular remodeling and pulmonary hypertension.Blood advances · 2025Article
- Immunotherapy for Pulmonary Arterial Hypertension: From the Pathogenesis to Clinical Management.International journal of molecular sciences · 2024Review
- Exploring the pathogenesis of pulmonary vascular disease.Frontiers in medicine · 2024Review
- 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
- Portopulmonary Hypertension: An Updated Review.Transplantation direct · 2023Review
- Vascular pathobiology of pulmonary hypertension.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2023Review
- Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension.Frontiers in immunology · 2023Review
- Review
- Nets, pulmonary arterial hypertension, and thrombo-inflammation.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Platelet and Megakaryocyte Roles in Innate and Adaptive Immunity.Circulation research · 2022Review
- TLR4-SIRT3 Mechanism Modulates Mitochondrial and Redox Homeostasis and Promotes EPCs Recruitment and Survival.Oxidative medicine and cellular longevity · 2022Article
- Role of Gut Microbiota in Pulmonary Arterial Hypertension.Frontiers in cellular and infection microbiology · 2022Review
- Comprehensive analysis and validation of novel immune and vascular remodeling related genes signature associated with drug interactions in pulmonary arterial hypertension.Frontiers in genetics · 2022Article
- Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Review
- Review
Corrections and comments
- Commented on by
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleRecent studies demonstrate a role for toll-like receptor 4 (TLR4) in the pathogenesis of pulmonary hypertension (PH); however, the cell types involved in mediating the effects of TLR4 remain unknown.
objectivesThe objective of this study was to determine the contribution of TLR4 expressed on nonparenchymal cells to the pathogenesis of PH. METHODS AND
resultsTLR4 bone marrow chimeric mice revealed an equal contribution of TLR4 on nonparenchymal and parenchymal cells in the pathogenesis of PH as determined by measuring right ventricular (RV) systolic pressure and RV hypertrophy. However, the deletion of TLR4 from myeloid lineage cells had no effect on the development of PH because we found no difference in RV systolic pressure or RV hypertrophy in wild-type versus LysM-TLR4(-/-) mice. To explore the potential role of platelet TLR4 in the pathogenesis of PH, platelet-specific TLR4(-/-) mice were generated (PF4-TLR4(-/-) mice). TLR4(-/-) platelets from either global TLR4(-/-) or PF4-TLR4(-/-) mice were functional but failed to respond to lipopolysaccharide, demonstrating a lack of TLR4. PF4-TLR4(-/-) mice demonstrated significant protection from hypoxia-induced PH, including attenuated increases in RV systolic pressure and RV hypertrophy, decreased platelet activation, and less pulmonary vascular remodeling. The deletion of TLR4 from platelets attenuated serotonin release after chronic hypoxia, and lipopolysaccharide-stimulated platelets released serotonin and promoted pulmonary artery smooth muscle cell proliferation in a serotonin-dependent manner.
conclusionsOur data demonstrate that TLR4 on platelets contributes to the pathogenesis of PH and further highlights the role of platelets in PH.
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.