ArticleJCI insight2025
An intracellular complement system drives metabolic and proinflammatory reprogramming of vascular fibroblasts in pulmonary hypertension.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed.
- GRAIL-heart: A graph attention network for inferring ligand-receptor interactions in spatial transcriptomics.MethodsX · 2026Article
- Interpreting Pulmonary Hypertension Beyond Single Cells.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.International journal of molecular sciences · 2026Review
- Adventitial Niches, Complement and Inflammation in Pulmonary Vascular Disease: Current Status and Future Directions.Comprehensive Physiology · 2026Review
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- Article
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- NF-κB signaling as a critical inflammatory node in pulmonary arterial hypertension: from vascular remodeling to right heart failure.Frontiers in immunology · 2026Review
- Vascular adventitial cells and vascular remodeling: when a harp of thousand strings does not keep in tune so long.Frontiers in physiology · 2026Review
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- A Lifelong Journey in the Field of the Pulmonary Circulation: Perspectives Through the Lens of the Cardiovascular Pulmonary Research Laboratory.Pulmonary circulation · 2025Article
- Complement C3 Activation in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025Article
- Single-cell RNA-seq analysis of mouse carotid artery under disturbed flow and human carotid plaques identifies key cell populations in atherosclerosis development.Scientific reports · 2025Article
- Dual role of complement in neuronal repair.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
The complement system is central to the innate immune response, playing a critical role in proinflammatory and autoimmune diseases such as pulmonary hypertension (PH). Recent discoveries highlight the emerging role of intracellular complement, or the "complosome," in regulating cellular processes such as glycolysis, mitochondrial dynamics, and inflammatory gene expression. This study investigated the hypothesis that intracellular complement proteins C3, CFB, and CFD are upregulated in PH fibroblasts (PH-Fibs) and drive their metabolic and inflammatory states, contributing to PH progression. Our results revealed a pronounced upregulation of CFD, CFB, and C3 in PH-Fibs from human samples and bovine models, both in vivo and in vitro. The finding of elevated levels of C3 activation fragments, including C3b, C3d, and C3a, emphasized enhanced C3 activity. PH-Fibs exhibited notable metabolic reprogramming and increased levels of proinflammatory mediators such as MCP1, SDF1, IL-6, IL-13, and IL-33. Silencing CFD via shRNA reduced CFB activation and C3a production, while normalizing glycolysis, tricarboxylic acid (TCA) cycle activity, and fatty acid metabolism. Metabolomic and gene expression analyses of CFD-knockdown PH-Fibs revealed restored metabolic and inflammatory profiles, underscoring CFD's crucial role in these changes. This study emphasizes the crucial role of intracellular complement in PH pathogenesis, highlighting the potential for complement-targeted therapies 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.