ArticleResearch and practice in thrombosis and haemostasis2021
Complement factor C4a does not activate protease-activated receptor 1 (PAR1) or PAR4 on human platelets.
Article in Research and practice in thrombosis and haemostasis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed, 9 citations in OpenAlex.
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Emerging Therapies in Hemophilia: Improving Equitable Access to Care.Journal of blood medicine · 2025Review
- Structural biology of complement receptors.Frontiers in immunology · 2023Review
- Complement and Coagulation System Crosstalk in Synaptic and Neural Conduction in the Central and Peripheral Nervous Systems.Biomedicines · 2021Review
- Complement factor C4a does not activate protease-activated receptor 1 (PAR1) or PAR4 on human platelets.Research and practice in thrombosis and haemostasis · 2021Article
- C1-inhibitor influence on platelet activation by thrombin receptors agonists.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProtease-activated receptor (PAR) 1 and PAR4 are key thrombin signal mediators for human platelet activation and aggregation in response to vascular injury. They are primarily activated by thrombin cleavage of the N-terminus to expose a tethered ligand. In addition to the canonical activation by thrombin, a growing panel of proteases can also elicit PAR1- or PAR4-mediated signal transduction. Recently, complement factor C4a was reported as the first endogenous agonist for both PAR1 and PAR4. Further, it is the first endogenous nontethered ligand that activates PAR1 and PAR4. These studies were conducted with human microvascular cells; the impact of C4a on platelet PARs is unknown.
objectivesThe goal of this study was to interrogate PAR1 and PAR4 activation by C4a on human platelets.
methodsPlatelet-rich plasma (PRP) was isolated from healthy donors. PRP was stimulated with C4a, and the platelet aggregation was measured. Human embryonic kidney (HEK) 293 Flp-In T-rex cells were used to further test if C4a stimulation can initiate PAR1- or PAR4-mediated Gα
resultsC4a failed to elicit platelet aggregation via PAR1- or PAR4-mediated manner. In addition, no PAR1- or PAR4-mediated calcium mobilization was observed upon C4a stimulation on HEK293 cells.
conclusionsComplement factor C4a does not activate PAR1 or PAR4 on human platelets. These data show that PAR1 and PAR4 activation by C4a on microvascular cells likely requires a cofactor, which reinforces the concept of cell type-specific regulation of protease signaling.
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.