ArticleCirculation2009
A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension.
Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- A systematic review of genetic mutations in pulmonary arterial hypertension.BMC medical genetics · 2017Pooled it
- Functional Role of Piezo1 in Regulating Whole-Lung Vascular Reactivity.Pulmonary circulation · 2026Article
- Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial CaArteriosclerosis, thrombosis, and vascular biology · 2026Review
- Review
- Impact of C-Terminal PKC Phosphorylation on TRPC6 Current Kinetics.International journal of molecular sciences · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Role of the Renin-Angiotensin System in Blood Pressure Regulation in Smooth Muscle-Specific Cullin-3 Deficient Mice.Hypertension (Dallas, Tex. : 1979) · 2025Article
- TRPC expression in human periodontal ligament cells and the periodontal tissue of periodontitis mice: a preliminary study.Laboratory animal research · 2023Article
- Transient Receptor Potential Canonical 6 (TRPC6) Channel in the Pathogenesis of Diseases: A Jack of Many Trades.Inflammation · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- Acute oxygen sensing by vascular smooth muscle cells.Frontiers in physiology · 2023Review
- Recent Advances in the Treatment of Pulmonary Arterial Hypertension.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Evaluation of the presence of TRPC6 channels in human vessels: A pilot study using immunohistochemistry.Biomedical reports · 2022Article
- Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2022Review
- Channelopathy Genes in Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension.American journal of physiology. Cell physiology · 2021Article
- TRPC6, a therapeutic target for pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2021Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundExcessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role in the development of idiopathic pulmonary arterial hypertension (IPAH), whereas a rise in cytosolic Ca2+ concentration triggers PASMC contraction and stimulates PASMC proliferation. Recently, we demonstrated that upregulation of the TRPC6 channel contributes to proliferation of PASMCs isolated from IPAH patients. This study sought to identify single-nucleotide polymorphisms (SNPs) in the TRPC6 gene promoter that are associated with IPAH and have functional significance in regulating TRPC6 activity in PASMCs. METHODS AND
resultsGenomic DNA was isolated from blood samples of 237 normal subjects and 268 IPAH patients. Three biallelic SNPs, -361 (A/T), -254(C/G), and -218 (C/T), were identified in the 2000-bp sequence upstream of the transcriptional start site of TRPC6. Although the allele frequencies of the -361 and -218 SNPs were not different between the groups, the allele frequency of the -254(C-->G) SNP in IPAH patients (12%) was significantly higher than in normal subjects (6%; P<0.01). Genotype data showed that the percentage of -254G/G homozygotes in IPAH patients was 2.85 times that of normal subjects. Moreover, the -254(C-->G) SNP creates a binding sequence for nuclear factor-kappaB. Functional analyses revealed that the -254(C-->G) SNP enhanced nuclear factor-kappaB-mediated promoter activity and stimulated TRPC6 expression in PASMCs. Inhibition of nuclear factor-kappaB activity attenuated TRPC6 expression and decreased agonist-activated Ca2+ influx in PASMCs of IPAH patients harboring the -254G allele.
conclusionsThese results suggest that the -254(C-->G) SNP may predispose individuals to an increased risk of IPAH by linking abnormal TRPC6 transcription to nuclear factor-kappaB, an inflammatory transcription factor.
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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.