ArticleJournal of thrombosis and haemostasis : JTH2024
Aging-related alterations in mechanistic target of rapamycin signaling promote platelet hyperreactivity and thrombosis.
Article in Journal of thrombosis and haemostasis : JTH, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Toward standardization and a concerted vision for platelet proteomics research: communication from the SSC of the ISTH.Journal of thrombosis and haemostasis : JTH · 2025Guideline
- Differential regulation of cyclic adenosine monophosphate by phosphodiesterase 3A discriminates thrombin-induced protease activated receptor 1- and 4-dependent platelet activation.Journal of thrombosis and haemostasis : JTH · 2026Article
- Platelet mTOR Is a Regulator of Sterile Immunothrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Aortotomy-induced acute mural thrombosis progresses to saccular aneurysm formation.Research and practice in thrombosis and haemostasis · 2026Article
- Age-multiplied low density lipoprotein cholesterol (LDL-C) burden (AM-LDL) index stratifies bleeding and ischemic risk in acute coronary syndrome: implications for early therapeutic intensification.Lipids in health and disease · 2025Article
- Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation.Circulation research · 2025Article
- Decoding the anti-thrombotic effects of leonurine: a multimodal approach combining TCM repositioning and mTOR signaling.Chinese medicine · 2025Article
- Demographic diversity in platelet function and response to antiplatelet therapy.Trends in pharmacological sciences · 2025Review
- ShSPI Inhibits Thrombosis Formation and Ischemic Stroke In Vivo.International journal of molecular sciences · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundAging is an independent risk factor for the development of cardiovascular, thrombotic, and other chronic diseases. However, mechanisms of platelet hyperactivation in aging remain poorly understood.
objectivesHere, we examine whether and how aging alters intracellular signaling in platelets to support platelet hyperactivity and thrombosis.
methodsQuantitative mass spectrometry with tandem mass tag labeling systematically measured protein phosphorylation in platelets from healthy aged (>65 years) and young human (<45 years) subjects. The role of platelet mechanistic target of rapamycin (mTOR) in aging-induced platelet hyperreactivity was assessed using pharmacologic mTOR inhibition and a platelet-specific mTOR-deficient mouse model (mTOR
resultsQuantitative phosphoproteomics uncovered differential site-specific protein phosphorylation within mTOR, Rho GTPase, and MAPK pathways in platelets from aged donors. Western blot confirmed constitutive activation of the mTOR pathway in platelets from both aged humans and mice, which was associated with increased aggregation compared with that in young controls. Inhibition of mTOR with either Torin 1 in aged humans or genetic deletion in aged mice reversed platelet hyperreactivity. In a collagen-epinephrine pulmonary thrombosis model, aged wild-type (mTOR
conclusionAging-related changes in mTOR phosphorylation enhance Rac1 and p38 activation to enhance thromboxane generation, platelet hyperactivity, and thrombosis.
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