ArticleAmerican journal of respiratory and critical care medicine2010
Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension.
Article in American journal of respiratory and critical care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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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
65 citing papers in PubMed, 133 citations in OpenAlex.
- Prostanoid EP₂ Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells.International journal of molecular sciences · 2018Trial
- Treprostinil Iontophoresis in Idiopathic Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2015Trial
- Evaluation of a new formulation of epoprostenol sodium in Japanese patients with pulmonary arterial hypertension (EPITOME4).Advances in therapy · 2013Trial
- G Protein-Coupled Receptor in High-Altitude Diseases: Mechanistic Insights and Therapeutic Opportunities.MedComm · 2026Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis.Reviews in cardiovascular medicine · 2025Review
- Empagliflozin Attenuates Pulmonary Arterial Remodeling Through Peroxisome Proliferator-Activated Receptor Gamma Activation.ACS pharmacology & translational science · 2024Article
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- Characteristic disease defects in circulating endothelial cells isolated from patients with pulmonary arterial hypertension.PloS one · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension.Metabolites · 2023Review
- Prostaglandin and prostaglandin receptors: present and future promising therapeutic targets for pulmonary arterial hypertension.Respiratory research · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2023Review
- Inactivating the Uninhibited: The Tale of Activins and Inhibins in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- A Bioinformatic Algorithm based on Pulmonary Endoarterial Biopsy for Targeted Pulmonary Arterial Hypertension Therapy.The open respiratory medicine journal · 2023Article
- Prostanoid Signaling in Cancers: Expression and Regulation Patterns of Enzymes and Receptors.Biology · 2022Article
- New strategy to resume and taper epoprostenol after lung transplant for pulmonary hypertension.General thoracic and cardiovascular surgery · 2022Article
- Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2022Review
- Disease-specific platelet signaling defects in idiopathic pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
rationaleProstacyclin analogs, used to treat idiopathic pulmonary arterial hypertension (IPAH), are assumed to work through prostacyclin (IP) receptors linked to cyclic AMP (cAMP) generation, although the potential to signal through peroxisome proliferator-activated receptor-γ (PPARγ) exists.
objectivesIP receptor and PPARγ expression may be depressed in IPAH. We wished to determine if pathways remain functional and if analogs continue to inhibit smooth muscle proliferation.
methodsWe used Western blotting to determine IP receptor expression in peripheral pulmonary arterial smooth muscle cells (PASMCs) from normal and IPAH lungs and immunohistochemistry to evaluate IP receptor and PPARγ expression in distal arteries. MEASUREMENTS AND MAIN
resultsCell proliferation and cAMP assays assessed analog responses in human and mouse PASMCs and HEK-293 cells. Proliferative rates of IPAH cells were greater than normal human PASMCs. IP receptor protein levels were lower in PASMCs from patients with IPAH, but treprostinil reduced replication and treprostinil-induced cAMP elevation appeared normal. Responses to prostacyclin analogs were largely dependent on the IP receptor and cAMP in normal PASMCs, although in IP(-/-) receptor cells analogs inhibited growth in a cAMP-independent, PPARγ-dependent manner. In IPAH cells, antiproliferative responses to analogs were insensitive to IP receptor or adenylyl cyclase antagonists but were potentiated by a PPARγ agonist and inhibited (∼ 60%) by the PPARγ antagonist GW9662. This coincided with increased PPARγ expression in the medial layer of acinar arteries.
conclusionsThe antiproliferative effects of prostacyclin analogs are preserved in IPAH despite IP receptor down-regulation and abnormal coupling. PPARγ may represent a previously unrecognized pathway by which these agents inhibit smooth muscle proliferation.
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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.