ArticleScientific reports2016
Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07422012 (Optimization of Tacrolimus Management During Pregnancy), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Optimization of Tacrolimus Management During Pregnancy: Modeling of Unbound and Whole Blood Tacrolimus in Pregnant Uterus Transplant Recipients
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Adverse Pregnancy Outcomes in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis.JAMA network open · 2024Pooled it
- Article
- Observational
- Immunosuppression and vascular remodeling after liver transplantation: Mechanisms, surrogate markers, and modifiable pathways.World journal of transplantation · 2026Review
- Systemic lupus erythematosus and pregnancy: a comprehensive clinical review of maternal, fetal, and treatment considerations.Advances in rheumatology (London, England) · 2026Review
- Early Proteomic Alterations in Non-segmental Vitiligo Skin Following Treatment with Topical Tacrolimus.Dermatology and therapy · 2026Article
- Systemic lupus erythematosus-accelerated atherosclerosis: mechanistic insights and clinical implications.Frontiers in immunology · 2026Review
- Immunosuppressants rewire the gut microbiome-alloimmune axis through time-dependent and tissue-specific mechanisms.Cell communication and signaling : CCS · 2025Article
- Analysis of 24-Hour Blood Pressure Profile and Antihypertensive Therapy in Male Heart Transplant Patients.Journal of clinical medicine · 2025Article
- Immunosuppressants Rewire the Gut Microbiome-Alloimmune Axis Through Time-Dependent and Tissue-Specific Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Article
- Tacrolimus-Induced Acute Esophageal Necrosis Postorthotopic Liver Transplantation.ACG case reports journal · 2025Article
- Unveiling the Therapeutic Potential of Dulaglutide in Mitigating Tacrolimus-Induced Nephrotoxicity Through Targeting the miR-22/HMGB-1/TLR4/MyD88/NF-κB Trajectory.Archiv der Pharmazie · 2025Article
- Article
- Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights.Open medicine (Warsaw, Poland) · 2025Article
- 3D Bioprinting of Cellular Therapeutic Systems in Ophthalmology: from Bioengineered Tissue to Personalized Drug Delivery.Current ophthalmology reports · 2025Review
- Drug-Induced Myocardial Infarction: A Review of Pharmacological Triggers and Pathophysiological Mechanisms.Journal of cardiovascular development and disease · 2024Review
- Cyclosporine successfully treats steroid-resistant checkpoint inhibitor-related pneumonitis: a case report.BMC pulmonary medicine · 2024Article
- Oxidative stress-induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk.Research and practice in thrombosis and haemostasis · 2024Article
- A retrospective analysis of the safety of tacrolimus use and its optimal cut-off concentration during pregnancy in women with systemic lupus erythematosus: study from two Japanese tertiary referral centers.Arthritis research & therapy · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The introduction of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus greatly reduced the rate of allograft rejection, although their chronic use is marred by a range of side effects, among them vascular toxicity. In transplant patients, it is proved that innate immunity promotes vascular injury triggered by ischemia-reperfusion damage, atherosclerosis and hypertension. We hypothesized that activation of the innate immunity and inflammation may contribute to CNI toxicity, therefore we investigated whether TLR4 mediates toxic responses of CNIs in the vasculature. Cyclosporine and tacrolimus increased the production of proinflammatory cytokines and endothelial activation markers in cultured murine endothelial and vascular smooth muscle cells as well as in ex vivo cultures of murine aortas. CNI-induced proinflammatory events were prevented by pharmacological inhibition of TLR4. Moreover, CNIs were unable to induce inflammation and endothelial activation in aortas from TLR4(-/-) mice. CNI-induced cytokine and adhesion molecules synthesis in endothelial cells occurred even in the absence of calcineurin, although its expression was required for maximal effect through upregulation of TLR4 signaling. CNI-induced TLR4 activity increased O2(-)/ROS production and NF-κB-regulated synthesis of proinflammatory factors in cultured as well as aortic endothelial and VSMCs. These data provide new insight into the mechanisms associated with CNI vascular inflammation.
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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.