ArticleCardiovascular research2014
Acetylation of cyclophilin A is required for its secretion and vascular cell activation.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- Plasma cyclophilin a as a novel predictor of major adverse cardiac events in patients with acute myocardial injury cohort study.BMC cardiovascular disorders · 2026Article
- Sirtuin 4 accelerates heart failure development by enhancing reactive oxygen species-mediated profibrotic transcriptional signaling.Journal of molecular and cellular cardiology plus · 2025Article
- Activity-Based Acylome Profiling withJournal of the American Chemical Society · 2024Article
- The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Co-translational Installation of Posttranslational Modifications by Non-canonical Amino Acid Mutagenesis.Chembiochem : a European journal of chemical biology · 2023Article
- Phosphorylation of the prolyl isomerase Cyclophilin A regulates its localisation and release from the centrosome during mitosis.Cell cycle (Georgetown, Tex.) · 2023Article
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma.International journal of molecular sciences · 2022Article
- Supra-lacrimal protein-based carriers for cyclosporine A reduce Th17-mediated autoimmunity in murine model of Sjögren's syndrome.Biomaterials · 2022Article
- Vascular hyperacetylation is associated with vascular smooth muscle dysfunction in a rat model of non-obese type 2 diabetes.Molecular medicine (Cambridge, Mass.) · 2022Article
- Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets.International journal of molecular sciences · 2022Article
- Abdominal Aortic Aneurysm Formation with a Focus on Vascular Smooth Muscle Cells.Life (Basel, Switzerland) · 2022Review
- Role of Posttranslational Modifications of Proteins in Cardiovascular Disease.Oxidative medicine and cellular longevity · 2022Review
- Current update on theranostic roles of cyclophilin A in kidney diseases.Theranostics · 2022Review
- Secreted Extracellular Cyclophilin A Is a Novel Mediator of Ventilator-induced Lung Injury.American journal of respiratory and critical care medicine · 2021Article
- Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth.Cellular microbiology · 2021Article
- Endothelial-to-Mesenchymal Transition and Inflammation Play Key Roles in Cyclophilin A-Induced Pulmonary Arterial Hypertension.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.International journal of molecular sciences · 2020Review
- Cyclophilin a signaling induces pericyte-associated blood-brain barrier disruption after subarachnoid hemorrhage.Journal of neuroinflammation · 2020Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsCyclophilin A (CyPA) is a pro-inflammatory mediator involved in oxidative stress-related cardiovascular diseases. It is secreted from vascular smooth muscle cell (VSMC) in response to reactive oxygen species (ROS) in a highly regulated manner. Extracellular CyPA activates VSMCs and endothelial cells (ECs) promoting inflammation, cell growth, and cell death. Recently, it was shown that acetylated CyPA (AcK-CyPA) affects its function. We investigated the role of acetylation of CyPA for its secretion and signalling in vascular cells. METHODS AND
resultsWe used angiotensin II (Ang II) to create sustained ROS and found significantly increased AcK-CyPA in VSMC. Site-directed mutagenesis showed that lysines K82 and K125 were the predominant CyPA residues acetylated in response to Ang II. Importantly, acetylation of K82 and K125 were required for Ang II-mediated CyPA secretion. ROS inhibitors, Tiron, and N-acetylcysteine inhibited Ang II-induced intracellular CyPA acetylation and also AcK-CyPA secretion. Using secreted CyPA from wild type and K82/125R mutants expressed in transduced VSMC or in vitro acetylated recombinant CyPA, we showed that extracellular AcK-CyPA significantly increased pERK1/2, matrix metalloproteinase-2 activation, and ROS production in VSMC compared with non-acetylated CyPA. Moreover, extracellular AcK-CyPA increased adhesion molecule expression (VCAM-1 and ICAM-1) in EC, which promoted monocyte adhesion.
conclusionsROS-dependent acetylation of CyPA is required for the generation of extracellular CyPA. Acetylated extracellular CyPA regulates VSMC and EC activation, suggesting that inhibition of acetylation of CyPA may prevent the pathogenesis of oxidative stress-related cardiovascular diseases.
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