ArticlePhysiological reports2013
Thrombin-mediated activation of Akt signaling contributes to pulmonary vascular remodeling in pulmonary hypertension.
Article in Physiological reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Cost-effective, user-friendly detection and preconcentration of thrombin on a sustainable paper-based electrochemical platform.Analytical and bioanalytical chemistry · 2025Article
- Antiproliferative effect of selexipag active metabolite MRE-269 on pulmonary arterial smooth muscle cells from patients with chronic thromboembolic pulmonary hypertension.Pulmonary circulation · 2023Article
- TRPC6, a therapeutic target for pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study.Thrombosis journal · 2021Article
- Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension.Scientific reports · 2021Article
- mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target.International journal of molecular sciences · 2021Review
- Pathologic role of peptidyl-prolyl isomerase Pin1 in pulmonary artery remodeling.American journal of translational research · 2021Article
- AKT-targeted anti-inflammatory activity ofJournal of ginseng research · 2018Article
- Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation.Molecular and cellular biochemistry · 2015Article
- Upregulation of canonical transient receptor potential channel in the pulmonary arterial smooth muscle of a chronic thromboembolic pulmonary hypertension rat model.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Article
- Deficiency of Akt1, but not Akt2, attenuates the development of pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Article
- Are anticoagulants still indicated in pulmonary arterial hypertension?Pulmonary circulationArticle
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) has been increasingly recognized as a common source of elevated pulmonary vascular resistance and pulmonary hypertension. It is clear that development of pulmonary thromboemboli is the inciting event for this process, yet it remains unclear why some patients have persistent pulmonary artery occlusion leading to distal pulmonary vascular remodeling and CTEPH. Thrombin, a serine protease, is an integral part of the common coagulation cascade, yet thrombin also has direct cellular effects through interaction with the family of PAR membrane receptors. This study is designed to determine the effects of thrombin on Akt signaling in pulmonary artery smooth muscle cells (PASMC) from normal humans and pulmonary hypertension patients. Thrombin treatment of PASMC resulted in a transient increase in Akt phosphorylation and had similar effects on the downstream targets of the Akt/mTOR pathway. Ca(2+) is shown to be required for Akt phosphorylation as well as serum starvation, a distinct effect compared to platelet-derived growth factor. Thrombin treatment was associated with a rise in intracellular [Ca(2+)] and enhanced store-operated calcium entry (SOCE). These effects lead to enhanced proliferation, which is more dramatic in both IPAH and CTEPH PASMC. Enhanced proliferation is also shown to be attenuated by inhibition of Akt/mTOR in CTEPH PASMC. Thrombin has direct effects on PASMC increasing intracellular [Ca(2+)] and PASMC proliferation, an effect attributed to Akt phosphorylation. The current results implicate the effects of thrombin in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) and CTEPH, which may potentially be a novel therapeutic target.
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