ArticleAmerican journal of respiratory cell and molecular biology2015
Notch Activation of Ca(2+) Signaling in the Development of Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- A meta-analysis of randomized controlled trials: evaluating the efficacy of isokinetic muscle strengthening training in improving knee osteoarthritis outcomes.Journal of orthopaedic surgery and research · 2025Pooled it
- E2F1 Drives Endothelial Arterial Programming in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Functional Role of Piezo1 in Regulating Whole-Lung Vascular Reactivity.Pulmonary circulation · 2026Article
- Vacuum-stabilized lung window enables real-time and simultaneous imaging of vascular and calcium responses to hypoxia in vivo.Respiratory research · 2026Article
- A novel explainable deep-learning approach for network analysis of epistatic interactions.NAR genomics and bioinformatics · 2026Article
- Integrative analysis of single-cell RNA sequencing, bulk RNA sequencing, and proteomic data identified NOTCH3 as a hub gene contributing to human intervertebral disc fibrosis.Scientific reports · 2026Article
- Advances in Novel Therapeutic Strategies for Pulmonary Arterial Hypertension.Canadian respiratory journal · 2026Review
- Piezo1 in heart failure: A new perspective from cytomechanical sensing to diverse cellular pathways.Molecular biology reports · 2025Review
- Investigation of the mechanism of hypertension caused by BTKi in the treatment of hematologic diseases.Frontiers in pharmacology · 2025Review
- Mitochondria as a primary determinant of angiogenic modality in pulmonary arterial hypertension.The Journal of experimental medicine · 2024Article
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin.Open medicine (Warsaw, Poland) · 2024Article
- Up-regulated expression of two-pore domain KFrontiers in cardiovascular medicine · 2024Article
- Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.International journal of molecular sciences · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Jagged/Notch proteins promote endothelial-mesenchymal transition-mediated pulmonary arterial hypertension via upregulation of the expression of GATAs.Journal of cellular and molecular medicine · 2023Article
- Notch Signaling in Acute Inflammation and Sepsis.International journal of molecular sciences · 2023Review
- Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.Frontiers in immunology · 2023Review
- Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery.British journal of pharmacology · 2023Article
- Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells.American journal of physiology. Cell physiology · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
Abstract
Hypoxic pulmonary vasoconstriction (HPV) is an important physiological response that optimizes the ventilation/perfusion ratio. Chronic hypoxia causes vascular remodeling, which is central to the pathogenesis of hypoxia-induced pulmonary hypertension (HPH). We have previously shown that Notch3 is up-regulated in HPH and that activation of Notch signaling enhances store-operated Ca(2+) entry (SOCE), an important mechanism that contributes to pulmonary arterial smooth muscle cell (PASMC) proliferation and contraction. Here, we investigate the role of Notch signaling in HPV and hypoxia-induced enhancement of SOCE. We examined SOCE in human PASMCs exposed to hypoxia and pulmonary arterial pressure in mice using the isolated perfused/ventilated lung method. Wild-type and canonical transient receptor potential (TRPC) 6(-/-) mice were exposed to chronic hypoxia to induce HPH. Inhibition of Notch signaling with a γ-secretase inhibitor attenuates hypoxia-enhanced SOCE in PASMCs and hypoxia-induced increase in pulmonary arterial pressure. Our results demonstrate that hypoxia activates Notch signaling and up-regulates TRPC6 channels. Additionally, treatment with a Notch ligand can mimic hypoxic responses. Finally, inhibition of TRPC6, either pharmacologically or genetically, attenuates HPV, hypoxia-enhanced SOCE, and the development of HPH. These results demonstrate that hypoxia-induced activation of Notch signaling mediates HPV and the development of HPH via functional activation and up-regulation of TRPC6 channels. Understanding the molecular mechanisms that regulate cytosolic free Ca(2+) concentration and PASMC proliferation is critical to elucidation of the pathogenesis of HPH. Targeting Notch regulation of TRPC6 will be beneficial in the development of novel therapies for pulmonary hypertension associated with hypoxia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.