ArticlePulmonary circulation
CREB depletion in smooth muscle cells promotes medial thickening, adventitial fibrosis and elicits pulmonary hypertension.
Article in Pulmonary circulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Orphan receptor GPR153 facilitates vascular damage responses by modulating cAMP levels, YAP/TAZ signaling, and NF-κB activation.Nature communications · 2025Article
- The Involvement ofNutrients · 2025Review
- Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism.Physiological reports · 2024Article
- Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.Vascular pharmacology · 2023Article
- PGC-1α-mediated angiogenesis prevents pulmonary hypertension in mice.JCI insight · 2023Article
- MicroRNA-212-5p, an anti-proliferative miRNA, attenuates hypoxia and sugen/hypoxia-induced pulmonary hypertension in rodents.Molecular therapy. Nucleic acids · 2022Article
- Evaluating the Role of lncRNAs in the Incidence of Cardiovascular Diseases in Androgenetic Alopecia Patients.Cardiovascular toxicology · 2022Review
- Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Zinc-mediated activation of CREB pathway in proliferation of pulmonary artery smooth muscle cells in pulmonary hypertension.Cell communication and signaling : CCS · 2021Article
- Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2020Review
- Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension.Pulmonary circulationArticle
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Levels of the cAMP-responsive transcription factor, CREB, are reduced in medial smooth muscle cells in remodeled pulmonary arteries from hypertensive calves and rats with chronic hypoxia-induced pulmonary hypertension. Here, we show that chronic hypoxia fails to promote CREB depletion in pulmonary artery smooth muscle cells or elicit significant remodeling of the pulmonary arteries in mice, suggesting that sustained CREB expression prevents hypoxia-induced pulmonary artery remodeling. This hypothesis was tested by generating mice, in which CREB was ablated in smooth muscle cells. Loss of CREB in smooth muscle cells stimulated pulmonary artery thickening, right ventricular hypertrophy, profound adventitial collagen deposition, recruitment of myeloid cells to the adventitia, and elevated right ventricular systolic pressure without exposure to chronic hypoxia. Isolated murine CREB-null smooth muscle cells exhibited serum-independent proliferation and hypertrophy in vitro and medium conditioned by CREB-null smooth muscle cells stimulated proliferation and expression of extracellular matrix proteins by adventitial fibroblasts. We conclude that CREB governs the pathologic switch from homeostatic, quiescent smooth muscle cells to proliferative, synthetic cells that drive arterial remodeling contributing to the development or pulmonary 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.