ArticleCirculation research2013
Chloroquine prevents progression of experimental pulmonary hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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156 citing papers in PubMed, 1 synthesis or guideline pooled it, 282 citations in OpenAlex.
- Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review.Molecules (Basel, Switzerland) · 2020Pooled it
- Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.European journal of cancer (Oxford, England : 1990) · 2017Trial
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Fisetin alleviates pulmonary arterial hypertension by inhibiting the TGF-β1/Smad 2/3 signaling pathway.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- DDX3X induces mesenchymal transition of endothelial cells by disrupting BMPR2 signaling.FEBS open bio · 2026Article
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview.Cells · 2025Review
- The gut microbiota metabolite trimethylamine N-oxide promotes cardiac hypertrophy by activating the autophagic degradation of SERCA2a.Communications biology · 2025Article
- Ambrisentan Retains Its Pro-Autophagic Activity on Human Pulmonary Artery Endothelial Cells Exposed to Hypoxia in an In Vitro Model Mimicking Diabetes.Journal of cellular and molecular medicine · 2025Article
- Inhibition of Sodium/Hydrogen Exchanger-1 in the Right Ventricle and Lung Dysfunction Induced by Experimental Pulmonary Arterial Hypertension in Rats.Journal of the American Heart Association · 2025Article
- Dysregulation of Mitochondrial in Pulmonary Hypertension-Related Right Ventricular Remodeling: Pathophysiological Features and Targeting Drugs.Reviews in cardiovascular medicine · 2025Review
- New therapies in pulmonary arterial hypertension: Recent insights.International journal of cardiology. Congenital heart disease · 2025Article
- Chloroquine Restores eNOS Signaling in Shunt Endothelial Cells via Inhibiting eNOS Uncoupling.International journal of molecular sciences · 2025Article
- Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.Science (New York, N.Y.) · 2025Article
- The Role of Ion Channels in Pulmonary Hypertension: A Review.Pulmonary circulation · 2025Review
- Hypoxia-induced TPC2 transcription and glycosylation aggravates pulmonary arterial hypertension by blocking autophagy flux.Scientific reports · 2024Article
- Targeting Soluble TGF-β Factors: Advances in Precision Therapy for Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2024Review
- Pulmonary Arterial Hypertension and TGF-β Superfamily Signaling: Focus on Sotatercept.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Superenhancer-driven circRNA Myst4 involves in pulmonary artery smooth muscle cell ferroptosis in pulmonary hypertension.iScience · 2024Article
- Article
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Abstract
rationalePulmonary arterial hypertension (PAH) is characterized by excessive proliferation and apoptosis resistance in pulmonary artery smooth muscle cells (PASMCs).
objectiveWe reasoned that chloroquine, based on its ability to inhibit autophagy and block lysosomal degradation of the bone morphogenetic protein type II receptor (BMPR-II), might exert beneficial effects in this disease. METHODS AND
resultsPAH was induced in male Sprague-Dawley rats by administering monocrotaline. The induction of PAH was associated with changes in lung expression of LC3B-II, ATG5, and p62, consistent with increased autophagy, and decreased BMPR-II protein expression. Administration of chloroquine prevented the development of PAH, right ventricular hypertrophy, and vascular remodelling after monocrotaline, and prevented progression of established PAH in this model. Similar results were obtained with hydroxychloroquine. Chloroquine treatment increased whole lung and PASMC p62 protein levels consistent with inhibition of autophagy, and increased levels of BMPR-II protein. Chloroquine inhibited proliferation and increased apoptosis of PASMCs in vivo. In cultured rat PASMCs we confirmed that chloroquine both inhibited autophagy pathways and increased expression of BMPR-II protein via lysosomal inhibition. Consistent with the in vivo findings, chloroquine inhibited the proliferation and stimulated apoptosis of rat PASMCs in vitro, with no effect on endothelial cell proliferation or survival. Moreover, direct inhibition of autophagy pathways by ATG5 small interfering RNA knockdown inhibited proliferation of rat PASMCs.
conclusionsChloroquine and hydroxychloroquine exert beneficial effects in experimental PAH. The mechanism of action includes inhibition of autophagy pathways and inhibition of lysosomal degradation of BMPR-II.
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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.