ArticleCirculation2014
Aberrant chloride intracellular channel 4 expression contributes to endothelial dysfunction in pulmonary arterial hypertension.
Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 86 citations in OpenAlex.
- RELM-β Augmented Hypoxia-Induced Pulmonary Hypertension Through Interacting with GIPC1, OR1N1 and CLIC4.Cardiovascular drugs and therapy · 2026Article
- Single-nucleus RNA sequencing reveals the pathological process and key transcription factor of sorafenib-induced cardiotoxicity.BMC medicine · 2026Article
- KLF6 activation marks an angiogenic and apoptosis resistant endothelial phenotype in pulmonary arterial hypertension.Communications biology · 2026Article
- Genetic determinants of insufficiency of the collateral circulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Implication of intracellular chloride channel in extracellular matrix remodeling in pressure-overloaded mice and patients with dilated cardiomyopathy.Physiological reports · 2026Article
- Transforming growth factor beta (TGF-β) induces type 1 interferon signalling in systemic sclerosis keratinocytes through the chloride intracellular channel 4 (CLIC4).Arthritis research & therapy · 2025Article
- Critical role of mitochondrial dynamics in chronic respiratory diseases and new therapeutic directions.Chinese medical journal · 2025Review
- CLIC1 Supports Mechanisms Related to Platelet Activation and Thrombosis.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Article
- Clic6 Deficiency Triggers Aberrant Apical Microvilli in RPE.Investigative ophthalmology & visual science · 2025Article
- ARF6 as a Novel Activator of HIF-2α in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Emerging Gene Therapy Based on Nanocarriers: A Promising Therapeutic Alternative for Cardiovascular Diseases and a Novel Strategy in Valvular Heart Disease.International journal of molecular sciences · 2025Review
- Chloride intracellular channel (CLIC) protein function in S1P-induced Rac1 activation requires membrane localization of the C-terminus, but not thiol-transferase nor ion channel activities.Frontiers in cell and developmental biology · 2025Article
- Intracellular Chloride Channels: A Rising Target in Lung Disease Research.Journal of respiratory biology and translational medicine · 2025Article
- The Role of Ion Channels in Pulmonary Hypertension: A Review.Pulmonary circulation · 2025Review
- Chloride ions in health and disease.Bioscience reports · 2024Review
- Crosstalk between tumor and stroma modifies CLIC4 cargo in extracellular vesicles.Journal of extracellular biology · 2023Article
- CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1.Respiratory research · 2023Article
- Article
- Hungry for Chloride: Reprogramming Endothelial Cell Metabolism in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundChloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodeled pulmonary vessels and plexiform lesions of patients with pulmonary arterial hypertension. CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension. METHODS AND
resultsCLIC4 protein expression was increased in plasma and blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension and in the pulmonary vascular endothelium of 3 rat models of pulmonary hypertension. CLIC4 gene deletion markedly attenuated the development of chronic hypoxia-induced pulmonary hypertension in mice. Adenoviral overexpression of CLIC4 in cultured human pulmonary artery endothelial cells compromised pulmonary endothelial barrier function and enhanced their survival and angiogenic capacity, whereas CLIC4 shRNA had an inhibitory effect. Similarly, inhibition of CLIC4 expression in blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension attenuated the abnormal angiogenic behavior that characterizes these cells. The mechanism of CLIC4 effects involves p65-mediated activation of nuclear factor-κB, followed by stabilization of hypoxia-inducible factor-1α and increased downstream production of vascular endothelial growth factor and endothelin-1.
conclusionIncreased CLIC4 expression is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension.
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