ArticleArteriosclerosis, thrombosis, and vascular biology2017
Extracellular Cyclophilin A, Especially Acetylated, Causes Pulmonary Hypertension by Stimulating Endothelial Apoptosis, Redox Stress, and Inflammation.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- PDE10A Inhibition Disrupts Lipid Droplet Formation and Sensitizes Macrophages to Ferroptosis after LPS treatment.bioRxiv : the preprint server for biology · 2025Article
- Differential Expression of Neurodegeneration-Related Genes in SH-SY5Y Neuroblastoma Cells Under the Influence of Cyclophilin A: Could the Enzyme be a Likely Trigger and Therapeutic Target for Alzheimer's Disease?Neurochemical research · 2024Article
- The effects of CypA on apoptosis: potential target for the treatment of diseases.Applied microbiology and biotechnology · 2024Review
- Copper-Based Nanoparticles for Effective Treatment Against Sepsis-Induced Lung Injury in Mice Model.International journal of nanomedicine · 2024Article
- Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review.Metabolites · 2023Review
- The mechanism of programmed death and endoplasmic reticulum stress in pulmonary hypertension.Cell death discovery · 2023Review
- The Next Generation of KRAS Targeting: Reasons for Excitement and Concern.Molecular cancer therapeutics · 2022Review
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- Celastrol: A Promising Agent Fighting against Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Targeting peptidyl-prolyl isomerase 1 in experimental pulmonary arterial hypertension.The European respiratory journal · 2022Article
- Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets.International journal of molecular sciences · 2022Article
- Current update on theranostic roles of cyclophilin A in kidney diseases.Theranostics · 2022Review
- Extracellular cyclophilins A and C induce dysfunction of pancreatic microendothelial cells.Frontiers in physiology · 2022Article
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Phosphodiesterase 10A Is a Key Mediator of Lung Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Carbonic anhydrase inhibition improves pulmonary artery reactivity and nitric oxide-mediated relaxation in sugen-hypoxia model of pulmonary hypertension.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- The role of cigarette smoke-induced pulmonary vascular endothelial cell apoptosis in COPD.Respiratory research · 2021Review
- Enhanced Proliferation of Ly6CJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Role of Cyclophilins in Inflammatory Bowel Disease and Colorectal Cancer.International journal of biological sciences · 2021Review
- Endothelial Cell-Derived SOOxidative medicine and cellular longevity · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveOxidative stress and inflammation play key roles in the development of pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted in response to oxidative stress and promotes inflammation and cardiovascular disease. Endothelial cell (EC) dysfunction is an early event in the pathogenesis of PAH. We evaluated the role of extracellular CypA in PAH and compared the effects of acetylated CypA (AcK-CypA, increased by oxidative stress) and CypA on EC dysfunction. APPROACH AND
resultsIn transgenic mice that express high levels of CypA in EC specifically, a PAH phenotype was observed at 3 months including increased right ventricular systolic pressure, α-smooth muscle actin expression in small arterioles, and CD45-positive cells in the lungs. Mechanistic analysis using cultured mouse pulmonary microvascular EC and human pulmonary microvascular EC showed that extracellular CypA and AcK-CypA stimulated EC inflammatory signals: increased VCAM1 (vascular cell adhesion molecule 1) and ICAM1 (intercellular adhesion molecule 1), phosphorylation of p65, and degradation of IkB. Extracellular CypA and AcK-CypA increased EC apoptosis measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, Apo-ONE assay, and caspase 3 cleavage. Oxidative stress stimulated CypA and AcK-CypA secretion, which further promoted EC oxidative stress. AcK-CypA, compared with CypA, stimulated greater increases in apoptosis, inflammation, and oxidative stress. MM284, a specific inhibitor of extracellular CypA, attenuated EC apoptosis induced by CypA and AcK-CypA.
conclusionsEC-derived CypA (especially AcK-CypA) causes PAH by a presumptive mechanism involving increased EC apoptosis, inflammation, and oxidative stress. Our results suggest that inhibiting secreted extracellular CypA is a novel therapeutic approach for PAH.
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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.