ArticleCirculation research2012
Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- The calcium-sensing receptor in sepsis and septic shock, mechanistic pathways and translational perspectives: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Pooled it
- Associations between echocardiographic findings and prospective changes in residual renal function in patients new to peritoneal dialysis.Scientific reports · 2019Trial
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Calcium-Sensing Receptor as a Novel Target for the Treatment of Idiopathic Pulmonary Fibrosis.Biomolecules · 2025Article
- Role of the calcium-sensing receptor in regulating vascular function.Journal of cell communication and signaling · 2025Review
- Growth factors involved in vascular remodeling in pulmonary arterial hypertension.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats.Physiological reports · 2025Article
- Expanding diverse horizons in smooth muscle research: a symposium review of "Muscle and Pathology/Health: Frontiers of Translational Research" at the 66th Annual Meeting of Japan Society of Smooth Muscle Research.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- Sinisan ameliorates early-life stress-induced depressive-like behaviors by repairing DRN synaptic damage through CaSR.Frontiers in pharmacology · 2025Article
- The Role of Ion Channels in Pulmonary Hypertension: A Review.Pulmonary circulation · 2025Review
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Au-modified ceria nanozyme prevents and treats hypoxia-induced pulmonary hypertension with greatly improved enzymatic activity and safety.Journal of nanobiotechnology · 2024Article
- Up-regulated expression of two-pore domain KFrontiers in cardiovascular medicine · 2024Article
- ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.The Journal of general physiology · 2023Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.Cell communication and signaling : CCS · 2022Article
- The Platelet-Derived Growth Factor Pathway in Pulmonary Arterial Hypertension: Still an Interesting Target?Life (Basel, Switzerland) · 2022Review
- An Integrative Transcriptomic Analysis Reveals EGFR Exon-19 E746-A750 Fragment Deletion Regulated miRNA, circRNA, mRNA and lncRNA Networks in Lung Carcinoma.International journal of general medicine · 2022Article
- Changes in the gut microbiome and metabolome in a rat model of pulmonary arterial hypertension.Bioengineered · 2021Article
- Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleA rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. Increased resting [Ca(2+)](cyt) and enhanced Ca(2+) influx have been implicated in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH).
objectiveWe examined whether the extracellular Ca(2+)-sensing receptor (CaSR) is involved in the enhanced Ca(2+) influx and proliferation in IPAH-PASMC and whether blockade of CaSR inhibits experimental pulmonary hypertension. METHODS AND
resultsIn normal PASMC superfused with Ca(2+)-free solution, addition of 2.2 mmol/L Ca(2+) to the perfusate had little effect on [Ca(2+)](cyt). In IPAH-PASMC, however, restoration of extracellular Ca(2+) induced a significant increase in [Ca(2+)](cyt). Extracellular application of spermine also markedly raised [Ca(2+)](cyt) in IPAH-PASMC but not in normal PASMC. The calcimimetic R568 enhanced, whereas the calcilytic NPS 2143 attenuated, the extracellular Ca(2+)-induced [Ca(2+)](cyt) rise in IPAH-PASMC. Furthermore, the protein expression level of CaSR in IPAH-PASMC was greater than in normal PASMC; knockdown of CaSR in IPAH-PASMC with siRNA attenuated the extracellular Ca(2+)-mediated [Ca(2+)](cyt) increase and inhibited IPAH-PASMC proliferation. Using animal models of pulmonary hypertension, our data showed that CaSR expression and function were both enhanced in PASMC, whereas intraperitoneal injection of the calcilytic NPS 2143 prevented the development of pulmonary hypertension and right ventricular hypertrophy in rats injected with monocrotaline and mice exposed to hypoxia.
conclusionsThe extracellular Ca(2+)-induced increase in [Ca(2+)](cyt) due to upregulated CaSR is a novel pathogenic mechanism contributing to the augmented Ca(2+) influx and excessive PASMC proliferation in patients and animals with pulmonary arterial hypertension.
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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.