ArticleCardiovascular research2015
PKC-β activation inhibits IL-18-binding protein causing endothelial dysfunction and diabetic atherosclerosis.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 70 citations in OpenAlex.
- Asymmetric dimethylarginine serum levels are associated with early mortality after allogeneic stem cell transplantation.Haematologica · 2019Trial
- Identification of PRKCB, NLRC4, and TNFSF10 as Key Regulators of the Lipid Metabolism-Autophagy Network in Atherosclerosis.Cell biochemistry and function · 2026Article
- IL-18 in atherosclerosis: context-dependent biology, human evidence, and translational challenges.Frontiers in cardiovascular medicine · 2026Review
- Chronic hyperglycemia and cardiovascular dysfunction: an in-depth exploration of metabolic and cellular pathways in type 2 diabetes mellitus.Cardiovascular diabetology. Endocrinology reports · 2025Review
- Critical role of the β isoform of protein kinase C (PKCβ) in angiotensin II-induced oxidative stress in vascular smooth muscle cells.Physiological reports · 2025Article
- Molecular and Pathophysiological Mechanisms Leading to Ischemic Heart Disease in Patients with Diabetes Mellitus.International journal of molecular sciences · 2025Review
- High Glucose Treatment Induces Nuclei Aggregation of Microvascular Endothelial Cells via theArteriosclerosis, thrombosis, and vascular biology · 2025Article
- Endothelial dysfunction in acute ischemic stroke: a review.Journal of neurology · 2025Review
- Protein kinase C and endothelial dysfunction in select vascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead.International journal of molecular sciences · 2024Review
- Glymphatic function and its influencing factors in different glucose metabolism states.World journal of diabetes · 2024Article
- Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction inJournal of molecular and cellular cardiology plus · 2024Article
- Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells.Journal of nanobiotechnology · 2023Article
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.Cardiovascular diabetology · 2023Review
- Exploring the application of sildenafil for high-fat diet-induced erectile dysfunction based on interleukin-18-mediated NLRP3/Caspase-1 signaling pathway.Sexual medicine · 2023Article
- Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease.International journal of molecular sciences · 2023Review
- A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis.Frontiers in microbiology · 2023Review
- Gut macrobiotic and its metabolic pathways modulate cardiovascular disease.Frontiers in microbiology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsClinical observations showed a correlation between accelerated atherosclerosis in diabetes and high plasmatic level of IL-18, a pro-inflammatory cytokine. IL-18 enhances the production of inflammatory cytokines and cellular adhesion molecules contributing to atherosclerotic plaque formation and instability. Previous studies indicated that protein kinase C (PKC)-β inhibition prevented macrophage-induced cytokine expression involved in diabetic (DM) atherosclerotic plaque development. However, the role of PKC-β activation on IL-18/IL-18-binding protein (IL-18BP) pathway causing endothelial dysfunction and monocyte adhesion in diabetes has never been explored. METHODS AND
resultsApoe(-/-) mice were rendered DM and fed with western diet containing ruboxistaurin (RBX), a PKC-β inhibitor. After 20 weeks, atherosclerotic plaque composition was quantified. Compared with non-diabetic, DM mice exhibited elevated atherosclerotic plaque formation, cholestoryl ester content and macrophage infiltration, as well as reduced IL-18BP expression in the aorta which was prevented with RBX treatment. Endothelial cells (ECs) and macrophages were exposed to normal or high glucose (HG) levels with or without palmitate and recombinant IL-18 for 24 h. The combined HG and palmitate condition was required to increase IL-18 expression and secretion in macrophages, while it reduced IL-18BP expression in EC causing up-regulation of the vascular cell adhesion molecule (VCAM)-1 and monocyte adhesion. Elevated VCAM-1 expression and monocyte adherence were prevented by siRNA, RBX, and IL-18 neutralizing antibody.
conclusionOur study unrevealed a new mechanism by which PKC-β activation promotes EC dysfunction caused by the de-regulation of the IL-18/IL-18BP pathway, leading to increased VCAM-1 expression, monocyte/macrophage adhesion, and accelerated atherosclerotic plaque formation in diabetes.
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.