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Updated: Jun 23, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Intraplatelet miRNA-126 regulates thrombosis and its reduction contributes to platelet inhibition
Lu-Jun Zhang1, Yang-Xi Hu2, Rong-Zhong Huang3
1Department of Cardiology, Shanghai Changhai Hospital, 168 Changhai Road, Shanghai 200433, China.
Aims:
MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear.
Methods And Results:
Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading, and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the phosphoinositide 3-kinase/protein kinase B pathway, enhancing platelet activation through activating the integrin αIIbβ3-mediated outside-in signalling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease in platelet activity.
Conclusion:
Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.
Insights
Intraplatelet microRNA-126 (miR-126) promotes platelet activity and thrombus formation. Its reduction during antiplatelet therapy contributes to platelet inhibition, impacting cardiovascular disease treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Thrombosis Research
Background:
- MicroRNA-126 (miR-126) is abundant in platelets and influences platelet activity.
- Circulating miR-126 levels decrease during antiplatelet therapy.
- The specific role of intraplatelet miR-126 in thrombosis and platelet inhibition is not fully understood.
Purpose of the Study:
- To investigate the role of intraplatelet miR-126 in thrombosis and platelet function.
- To elucidate the mechanism by which miR-126 regulates platelet activation.
- To assess the impact of miR-126 levels on myocardial infarction (MI) progression and antiplatelet therapy efficacy.
Main Methods:
- Utilized tissue-specific knockout and chimeric mice to study miR-126 deficiency in platelets and vascular endothelial cells.
- Performed ex vivo experiments to assess platelet aggregation, spreading, and secretory functions.
- Investigated miR-126's molecular targets and signaling pathways, including PIK3R2 and the PI3K/Akt pathway.
- Analyzed miR-126 levels in patients with cardiovascular diseases undergoing antiplatelet therapy.
Main Results:
- Platelet-specific miR-126 deficiency significantly prevented thrombosis and prolonged bleeding time in mice.
- miR-126-deficient platelets showed impaired aggregation, spreading, and secretion.
- miR-126 targets PIK3R2, negatively regulating PI3K/Akt signaling and enhancing platelet activation.
- Lack of intraplatelet miR-126 reduced microvascular obstruction and MI expansion in vivo.
- Overexpression of miR-126 aggravated MI, an effect blunted by aspirin.
- Antiplatelet therapies (aspirin, clopidogrel) reduced intraplatelet miR-126 levels in patients, correlating with decreased platelet activity.
Conclusions:
- Intraplatelet miR-126 is a key contributor to platelet activity and thrombus formation.
- Reduced intraplatelet miR-126 levels are associated with platelet inhibition during antiplatelet therapy.
- These findings highlight miR-126 as a potential therapeutic target in cardiovascular diseases.
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