ArticlePloS one2014
Regulation of thrombomodulin expression and release in human aortic endothelial cells by cyclic strain.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Thrombomodulin and High-Sensitive C-Reactive Protein Levels in Blood Correlate with the Development of Cerebral Infarction Among Asians.Molecular neurobiology · 2016Pooled it
- The effects of balanced crystalloid versus plasma on endothelial injury, systemic inflammation, and coagulation in experimental endotoxaemia: a randomised human volunteer study.British journal of anaesthesia · 2026Trial
- Gene expression of thrombomodulin, TNF-α and NF-KB in coronary artery disease patients of Pakistan.Molecular biology reports · 2020Trial
- Article
- Uniaxial cyclic stretch regulates the expression of thrombomodulin and von Willebrand factor on endothelial cells.Blood vessels, thrombosis & hemostasis · 2025Article
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
- Association of Thrombomodulin Expression with Bladder Cancer Grade, Stage, and Recurrence: A Single-Center Prospective Pilot Study.Iranian journal of pathology · 2025Article
- Thrombomodulin (p.Cys537Stop) is released from cells by an unusual membrane insertion/leakage mechanism.Blood advances · 2024Article
- Poly (ADP-ribose) Polymerase-1 modulations in the genesis of thrombosis.Journal of thrombosis and thrombolysis · 2024Review
- Investigation of cofactor activities of endothelial microparticle-thrombomodulin with liposomal surrogate.Biochemical and biophysical research communications · 2023Article
- Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures.TH open : companion journal to thrombosis and haemostasis · 2022Review
- The role of endothelial shear stress on haemodynamics, inflammation, coagulation and glycocalyx during sepsis.Journal of cellular and molecular medicine · 2020Review
- Effects of probucol on atherosclerotic plaque and soluble thrombomodulin in patients with coronary heart disease.Experimental and therapeutic medicine · 2018Article
- Vascular endothelium - Gatekeeper of vessel health.Atherosclerosis · 2016Review
- Endothelial cell control of thrombosis.BMC cardiovascular disorders · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThrombomodulin (TM), an integral membrane glycoprotein expressed on the lumenal surface of vascular endothelial cells, promotes anti-coagulant and anti-inflammatory properties. Release of functional TM from the endothelium surface into plasma has also been reported. Much is still unknown however about how endothelial TM is regulated by physiologic hemodynamic forces (and particularly cyclic strain) intrinsic to endothelial-mediated vascular homeostasis.
methodsThis study employed human aortic endothelial cells (HAECs) to investigate the effects of equibiaxial cyclic strain (7.5%, 60 cycles/min, 24 hrs), and to a lesser extent, laminar shear stress (10 dynes/cm2, 24 hrs), on TM expression and release. Time-, dose- and frequency-dependency studies were performed.
resultsOur initial studies demonstrated that cyclic strain strongly downregulated TM expression in a p38- and receptor tyrosine kinase-dependent manner. This was in contrast to the upregulatory effect of shear stress. Moreover, both forces significantly upregulated TM release over a 48 hr period. With continuing focus on the cyclic strain-induced TM release, we noted both dose (0-7.5%) and frequency (0.5-2.0 Hz) dependency, with no attenuation of strain-induced TM release observed following inhibition of MAP kinases (p38, ERK-1/2), receptor tyrosine kinase, or eNOS. The concerted impact of cyclic strain and inflammatory mediators on TM release from HAECs was also investigated. In this respect, both TNFα (100 ng/ml) and ox-LDL (10-50 µg/ml) appeared to potentiate strain-induced TM release. Finally, inhibition of neither MMPs (GM6001) nor rhomboids (3,4-dichloroisocoumarin) had any effect on strain-induced TM release. However, significantly elevated levels (2.1 fold) of TM were observed in isolated microparticle fractions following 7.5% strain for 24 hrs.
conclusionsA preliminary in vitro investigation into the effects of cyclic strain on TM in HAECs is presented. Physiologic cyclic strain was observed to downregulate TM expression, whilst upregulating in a time-, dose- and frequency-dependent manner the release of TM.
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