ArticleThe Journal of clinical investigation2011
Calpain mediates pulmonary vascular remodeling in rodent models of pulmonary hypertension, and its inhibition attenuates pathologic features of disease.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 115 citations in OpenAlex.
- Amonafide Targeting NTSR1-PI3K/AKT/mTOR Signaling Attenuates Vascular Remodeling in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2026Article
- LncRNA-536 and RNA-Binding Protein RBM25 Interactions in Pulmonary Artery Smooth Muscle Cells: Implications in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Hypoxanthine Promotes Pulmonary Vascular Remodeling and Adenosine Deaminase Is a Therapeutic Target for Pulmonary Hypertension.JACC. Basic to translational science · 2025Article
- Limited Proteolysis as a Regulator of Lymphatic Vessel Function and Architecture.International journal of molecular sciences · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- The mitochondrial unfolded protein response and metabolic reprogramming promote PASMC proliferation in response to sphingosine kinase-1/sphingosine-1-phosphate signaling.bioRxiv : the preprint server for biology · 2025Article
- Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension.The Journal of clinical investigation · 2025Article
- Targeting PDGF/PDGFR Signaling Pathway by microRNA, lncRNA, and circRNA for Therapy of Vascular Diseases: A Narrow Review.Biomolecules · 2024Review
- Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models.iScience · 2024Article
- 5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase promotes pulmonary arterial smooth muscle cell proliferation via the Ras signaling pathway.American journal of physiology. Cell physiology · 2024Article
- The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis.Molecular cancer · 2024Article
- Calpain Promotes LPS-induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin.American journal of respiratory cell and molecular biology · 2023Article
- Intratracheally Administered Peptide-Modified Lipid Admixture Containing Fasudil and/or DETA NONOate Ameliorates Various Pathologies of Pulmonary Arterial Hypertension.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Sphingosine Kinase 1 Deficiency in Smooth Muscle Cells Protects against Hypoxia-Mediated Pulmonary Hypertension via YAP1 Signaling.International journal of molecular sciences · 2022Article
- Transgelin exacerbates pulmonary artery smooth muscle cell dysfunction in shunt-related pulmonary arterial hypertension.ESC heart failure · 2022Article
- Inhibition of KIR2.1 decreases pulmonary artery smooth muscle cell proliferation and migration.International journal of molecular medicine · 2022Article
- Myeloid cell-specific deletion of Capns1 prevents macrophage polarization toward the M1 phenotype and reduces interstitial lung disease in the bleomycin model of systemic sclerosis.Arthritis research & therapy · 2022Article
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Pulmonary hypertension is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Several growth factors, including EGF, PDGF, and TGF-β1, are involved in pulmonary vascular remodeling during pulmonary hypertension. However, increased knowledge of the downstream signaling cascades is needed if effective clinical interventions are to be developed. In this context, calpain provides an interesting candidate therapeutic target, since it is activated by EGF and PDGF and has been reported to activate TGF-β1. Thus, in this study, we examined the role of calpain in pulmonary vascular remodeling in two rodent models of pulmonary hypertension. These data showed that attenuated calpain activity in calpain-knockout mice or rats treated with a calpain inhibitor resulted in prevention of increased right ventricular systolic pressure, right ventricular hypertrophy, as well as collagen deposition and thickening of pulmonary arterioles in models of hypoxia- and monocrotaline-induced pulmonary hypertension. Additionally, inhibition of calpain in vitro blocked intracellular activation of TGF-β1, which led to attenuated Smad2/3 phosphorylation and collagen synthesis. Finally, smooth muscle cells of pulmonary arterioles from patients with pulmonary arterial hypertension showed higher levels of calpain activation and intracellular active TGF-β. Our data provide evidence that calpain mediates EGF- and PDGF-induced collagen synthesis and proliferation of pulmonary artery smooth muscle cells via an intracrine TGF-β1 pathway in 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.