ArticleHypertension (Dallas, Tex. : 1979)2016
Monocrotaline-Induced Pulmonary Hypertension Involves Downregulation of Antiaging Protein Klotho and eNOS Activity.
Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review.Stem cell research & therapy · 2019Pooled it
- Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants.Scientific reports · 2020Trial
- Fibulin 2 Deficiency Drives Epigenetic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
- Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model.Stem cell research & therapy · 2025Article
- Mesenchymal stem cell therapy for pulmonary hypertension: an update.Frontiers in bioengineering and biotechnology · 2025Review
- Enhanced Therapeutic Effects of Human Mesenchymal stem Cells Transduced with Secreted Klotho in a Murine Experimental Autoimmune Encephalomyelitis Model.Molecular neurobiology · 2024Article
- Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.Nature reviews. Nephrology · 2024Review
- Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Aging impairs arterial compliance via Klotho-mediated downregulation of B-cell population and IgG levels.Cellular and molecular life sciences : CMLS · 2022Article
- Stem cell therapy for pulmonary arterial hypertension: An update.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Review
- In Vivo Cardiac-specific Expression of Adenylyl Cyclase 4 Gene Protects against Klotho Deficiency-induced Heart Failure.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Regenerative Medicine Application of Mesenchymal Stem Cells.Advances in experimental medicine and biology · 2022Article
- Estrogen inhibits renal Na-Pi Co-transporters and improves klotho deficiency-induced acute heart failure.Redox biology · 2021Article
- Anti-Inflammatory Effect of Allicin Associated with Fibrosis in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway.Circulation research · 2021Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The objective of this study is to investigate whether stem cell delivery of secreted Klotho (SKL), an aging-suppressor protein, attenuates monocrotaline-induced pulmonary vascular dysfunction and remodeling. Overexpression of SKL in mesenchymal stem cells (MSCs) was achieved by transfecting MSCs with lentiviral vectors expressing SKL-green fluorescent protein (GFP). Four groups of rats were treated with monocrotaline, whereas an additional group was given saline (control). Three days later, 4 monocrotaline-treated groups received intravenous delivery of nontransfected MSCs, MSC-GFP, MSC-SKL-GFP, and PBS, respectively. Ex vivo vascular relaxing responses to acetylcholine were diminished in small pulmonary arteries (PAs) in monocrotaline-treated rats, indicating pulmonary vascular endothelial dysfunction. Interestingly, delivery of MSCs overexpressing SKL (MSC-SKL-GFP) abolished monocrotaline-induced pulmonary vascular endothelial dysfunction and PA remodeling. Monocrotaline significantly increased right ventricular systolic blood pressure, which was attenuated significantly by MSC-SKL-GFP, indicating improved PA hypertension. MSC-SKL-GFP also attenuated right ventricular hypertrophy. Nontransfected MSCs slightly, but not significantly, improved PA hypertension and pulmonary vascular endothelial dysfunction. MSC-SKL-GFP attenuated monocrotaline-induced inflammation, as evidenced by decreased macrophage infiltration around PAs. MSC-SKL-GFP increased SKL levels, which rescued the downregulation of SIRT1 (Sirtuin 1) expression and endothelial NO synthase (eNOS) phosphorylation in the lungs of monocrotaline-treated rats. In cultured endothelial cells, SKL abolished monocrotaline-induced downregulation of eNOS activity and NO levels and enhanced cell viability. Therefore, stem cell delivery of SKL is an effective therapeutic strategy for pulmonary vascular endothelial dysfunction and PA remodeling. SKL attenuates monocrotaline-induced PA remodeling and PA smooth muscle cell proliferation, likely by reducing inflammation and restoring SIRT1 levels and eNOS activity.
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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.