ArticlePulmonary circulation
Activation of the unfolded protein response is associated with 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 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- Sotatercept Reverses SIN3a Deficiency-Driven PAH by Reprogramming BMPR2/TGF-β-HIF-1α Signaling Pathways.bioRxiv : the preprint server for biology · 2026Article
- NF-κB signaling as a critical inflammatory node in pulmonary arterial hypertension: from vascular remodeling to right heart failure.Frontiers in immunology · 2026Review
- Emerging insights into pulmonary hypertension: the potential role of mitochondrial dysfunction and redox homeostasis.Molecular and cellular biochemistry · 2025Review
- Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.Circulation · 2024Article
- Identification of differentially expressed ER stress-related genes and their association with pulmonary arterial hypertension.Respiratory research · 2024Article
- Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease.Nature communications · 2023Article
- HMGB1-induced activation of ER stress contributes to pulmonary artery hypertension in vitro and in vivo.Respiratory research · 2023Article
- Hypoxia and the integrated stress response promote pulmonary hypertension and preeclampsia: Implications in drug development.Drug discovery today · 2021Review
- Effect of pulsatile stretch on unfolded protein response in a new model of the pulmonary hypertensive vascular wall.Biochemistry and biophysics reports · 2021Article
- Redox and Inflammatory Signaling, the Unfolded Protein Response, and the Pathogenesis of Pulmonary Hypertension.Advances in experimental medicine and biology · 2021Article
- [Advances in molecular mechanism of vascular remodeling in pulmonary arterial hypertension].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2019Review
- Article
- Emerging Metabolic Therapies in Pulmonary Arterial Hypertension.Journal of clinical medicine · 2017Review
- 4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats.PloS one · 2016Article
- The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- Proteostasis in pediatric pulmonary pathology.Molecular and cellular pediatrics · 2014Article
- Differential hypoxic tolerance is mediated by activation of heat shock response and nitric oxide pathway.Cell stress & chaperones · 2014Article
- Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.Circulation research · 2014Review
- Relevant issues in the pathology and pathobiology of pulmonary hypertension.Journal of the American College of Cardiology · 2013Review
- The UPR and lung disease.Seminars in immunopathology · 2013Review
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Pulmonary hypertension remains an important cause of morbidity and mortality. Although there is currently no cure, descriptions of defective intracellular trafficking and protein misfolding in vascular cell models of pulmonary hypertension have been recently reported. We tested the hypothesis that activation of the unfolded protein response (UPR) would be associated with the development of severe PH. We investigated activation of the UPR in archival tissues from patients with severe PH, and in the monocrotaline-induced rat model of severe PH. We tested the ability of a pharmacologic agent capable of modulating the UPR to prevent and reverse pulmonary hypertension. We found evidence of an active UPR in archival tissue from humans with PH, but not in control lungs. Similarly, monocrotaline-treated rats demonstrated a significant difference in expression of each of the major arms of the UPR compared to controls. Interestingly, the UPR preceded the appearance of macrophages and the development of lung vascular remodeling in the rats. Treatment of monocrotaline rats with salubrinal, a modulator of the PERK arm of the UPR, attenuated PH and was associated with a decrease in lung macrophages. In culture, pulmonary artery smooth muscle cells with UPR induction produced IL-6 and CCL-2/MCP-1, and stimulated macrophage migration. These effects were abolished by pretreatment of cells with salubrinal. These data support the hypothesis that the UPR may play a role in the pathogenesis of inflammatory vascular remodeling and PH. As such, understanding the functional contributions of the UPR in the setting of PH may have important therapeutic implications.
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