ArticlePloS one2015
A critical role for the transient receptor potential channel type 6 in human platelet activation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Complications and thromboembolic events associated with tamoxifen therapy in patients with breast cancer undergoing microvascular breast reconstruction: a systematic review and meta-analysis.Breast cancer research and treatment · 2017Pooled it
- Ozone protects against ischemia-reperfusion injury: molecular mechanisms.Frontiers in pharmacology · 2026Review
- Platelet mitochondria dysfunction in diabetes mellitus: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6.Advances in experimental medicine and biology · 2023Article
- Identification of novel off targets of baricitinib and tofacitinib by machine learning with a focus on thrombosis and viral infection.Scientific reports · 2022Article
- The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis.International journal of molecular sciences · 2022Article
- TRPC6, a therapeutic target for pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- NEDD9, a Hypoxia-upregulated Mediator for Pathogenic Platelet-Endothelial Cell Interaction in Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2021Article
- New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice.Clinical reviews in allergy & immunology · 2021Review
- Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke.International journal of molecular sciences · 2021Review
- Control the platelets, control the disease: A novel cystic fibrosis hypothesis.Journal of thrombosis and haemostasis : JTH · 2020Article
- Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation.The Journal of clinical investigation · 2020Article
- Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury.JVS-vascular science · 2020Article
- Mouse transient receptor potential channel type 6 selectively regulates agonist-induced platelet function.Biochemistry and biophysics reports · 2019Article
- Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis.Journal of the American Heart Association · 2019Article
- Review
- Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD.PloS one · 2017Article
- Transcriptomic analysis of the ion channelome of human platelets and megakaryocytic cell lines.Thrombosis and haemostasis · 2016Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While calcium signaling is known to play vital roles in platelet function, the mechanisms underlying its receptor-operated calcium entry component (ROCE) remain poorly understood. It has been proposed, but never proven in platelets, that the canonical transient receptor potential channel-6 (TRPC6) mediates ROCE. Nonetheless, we have previously shown that the mouse TRPC6 regulates hemostasis, thrombogenesis by regulating platelet aggregation. In the present studies, we used a pharmacological approach to characterize the role of TRPC6 in human platelet biology. Thus, interestingly, we observed that a TRPC6 inhibitor exerted significant inhibitory effects on human platelet aggregation in a thromboxane receptor (TPR)-selective manner; no additional inhibition was observed in the presence of the calcium chelator BAPTA. This inhibitor also significantly inhibited human platelet secretion (dense and alpha granules), integrin IIb-IIIa, Akt and ERK phosphorylation, again, in a TPR-selective manner; no effects were observed in response to ADP receptor stimulation. Furthermore, there was a causal relationship between these inhibitory effects, and the capacity of the TRPC6 inhibitor to abrogate elevation in intracellular calcium, that was again found to be TPR-specific. This effect was not found to be due to antagonism of TPR, as the TRPC6 inhibitor did not displace the radiolabeled antagonist [3H]SQ29,548 from its binding sites. Finally, our studies also revealed that TRPC6 regulates human clot retraction, as well as physiological hemostasis and thrombus formation, in mice. Taken together, our findings demonstrate, for the first time, that TRPC6 directly regulates TPR-dependent ROCE and platelet function. Moreover, these data highlight TRPC6 as a novel promising therapeutic strategy for managing thrombotic disorders.
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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.