ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
Resveratrol prevents hypoxia-induced arginase II expression and proliferation of human pulmonary artery smooth muscle cells via Akt-dependent signaling.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Dose-related Effects of Resveratrol in Different Models of Pulmonary Arterial Hypertension: A Systematic Review.Current cardiology reviews · 2020Pooled it
- Licoisoflavone A potentiates oxaliplatin efficacy in colorectal cancer by dual targeting arginine metabolism of tumor microenvironment and cancer cells.Chinese medicine · 2026Article
- Resveratrol and Its Nitric Oxide-Donor Hybrid as an Emerging Therapy for Oxidative-Stress-Driven Priapism in Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Matrix metalloproteinase-3 promotes arteriovenous fistula failure by regulating FAK-AKT signaling.bioRxiv : the preprint server for biology · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Arginase-II promotes melanoma and lung cancer cell growth by regulating Sirt3-mtROS axis.Frontiers in cell and developmental biology · 2025Article
- Chinese Herbal Medicine in Hypoxic Pulmonary Hypertension Treatment: Mechanisms, Progress, and Future Directions.Drug design, development and therapy · 2025Review
- Pulmonary hypertension: etiology and anti-inflammatory treatment pathways of natural products.Frontiers in pharmacology · 2025Review
- Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions.Frontiers in pharmacology · 2025Review
- Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism.Physiological reports · 2024Article
- Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition.International journal of molecular sciences · 2024Review
- The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.Biological research · 2023Article
- Unleashing the Potential of Nrf2: A Novel Therapeutic Target for Pulmonary Vascular Remodeling.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Natural Products for the Treatment of Pulmonary Hypertension: Mechanism, Progress, and Future Opportunities.Current issues in molecular biology · 2023Review
- Therapeutic Potential of Select Dietary Compounds in the Management of Hypertension and its Cardiovascular Complications.Molecules (Basel, Switzerland) · 2022Review
- Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases.Cell death discovery · 2022Review
- Disease-associated regulation of gene expression by resveratrol: Special focus on the PI3K/AKT signaling pathway.Cancer cell international · 2022Review
- Epigenetic Mechanisms as Emerging Therapeutic Targets and Microfluidic Chips Application in Pulmonary Arterial Hypertension.Biomedicines · 2022Review
- PGC-1α activity and mitochondrial dysfunction in preterm infants.Frontiers in physiology · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pulmonary artery smooth muscle cell (PASMC) proliferation plays a fundamental role in the vascular remodeling seen in pulmonary hypertensive diseases associated with hypoxia. Arginase II, an enzyme regulating the first step in polyamine and proline synthesis, has been shown to play a critical role in hypoxia-induced proliferation of human PASMC (hPASMC). In addition, there is evidence that patients with pulmonary hypertension have elevated levels of arginase in the vascular wall. Resveratrol, a natural polyphenol found in red wine and grape skins, has diverse biochemical and physiological actions including antiproliferative properties. Furthermore, resveratrol has been shown to attenuate right ventricular and pulmonary artery remodeling, both pathological components of pulmonary hypertension. The present studies tested the hypothesis that resveratrol would prevent hypoxia-induced pulmonary artery smooth muscle cell proliferation by inhibiting hypoxia-induced arginase II expression. Our data indicate that hypoxia-induced hPASMC proliferation is abrogated following treatment with resveratrol. In addition, the hypoxic induction of arginase II was directly attenuated by resveratrol treatment. Furthermore, we found that the inhibitory effect of resveratrol on arginase II in hPASMC was mediated through the PI3K-Akt signaling pathway. Supporting these in vitro findings, resveratrol normalized right ventricular hypertrophy in an in vivo neonatal rat model of chronic hypoxia-induced pulmonary hypertension. These novel data support the notion that resveratrol may be a potential therapeutic agent in pulmonary hypertension by preventing PASMC arginase II induction and proliferation.
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