ArticleAmerican journal of physiology. Lung cellular and molecular physiology2008
High levels of hyaluronan in idiopathic pulmonary arterial hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- An official American Thoracic Society Statement: pulmonary hypertension phenotypes.American journal of respiratory and critical care medicine · 2014Guideline
- Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension.Thorax · 2025Trial
- Vascular EC-SOD limits the accumulation, proinflammatory profibrotic reprogramming, and hyaluronan binding of interstitial macrophages in hypoxia.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Identification of differentially expressed ER stress-related genes and their association with pulmonary arterial hypertension.Respiratory research · 2024Article
- Elevated Urine Hyaluronan Concentrations Are Associated with an Unfavorable Respiratory Outcome in Preterm Neonates at 40 Weeks Postmenstrual Age.Neonatology · 2024Article
- CPAP-induced airway hyper-reactivity in mice is modulated by hyaluronan synthase-3.Pediatric research · 2022Article
- 3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- The Glycobiology of Pulmonary Arterial Hypertension.Metabolites · 2022Review
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Detection of Glycosaminoglycans in Pancreatic Islets and Lymphoid Tissues.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Metabolic reprogramming: A novel metabolic model for pulmonary hypertension.Frontiers in cardiovascular medicine · 2022Review
- Basement Membrane Extracellular Matrix Proteins in Pulmonary Vascular and Right Ventricular Remodeling in Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2021Article
- Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets.International journal of molecular sciences · 2020Review
- Specific O-GlcNAc modification at Ser-615 modulates eNOS function.Redox biology · 2020Article
- Vascular Metabolic Mechanisms of Pulmonary Hypertension.Current medical science · 2020Review
- Extracellular Superoxide Dismutase Regulates Early Vascular Hyaluronan Remodeling in Hypoxic Pulmonary Hypertension.Scientific reports · 2020Article
- miR‑760 mediates hypoxia-induced proliferation and apoptosis of human pulmonary artery smooth muscle cells via targeting TLR4.International journal of molecular medicine · 2018Article
- High molecular weight hyaluronan ameliorates allergic inflammation and airway hyperresponsiveness in the mouse.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Micro-RNA-1 is decreased by hypoxia and contributes to the development of pulmonary vascular remodeling via regulation of sphingosine kinase 1.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis.British journal of pharmacology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Hyaluronan (HA), a large glycosaminoglycan found in the ECM, has major roles in lung and vascular biology and disease. However, its role in idiopathic pulmonary arterial hypertension (IPAH) is unknown. We hypothesized that HA metabolism is abnormal in IPAH. We measured the plasma levels of HA in IPAH and healthy individuals. We also evaluated HA synthesis and the expression of HA synthases and hyaluronidases in pulmonary artery smooth muscle cells (PASMCs) from explanted lungs. Plasma HA levels were markedly elevated in IPAH compared with controls [HA (ng/ml, mean +/- SD): IPAH 325 +/- 80, control 28 +/- 9; P = 0.02]. In vitro, unstimulated IPAH PASMCs produced high levels of HA compared with control cells [HA in supernatant (microg/ml, mean +/- SD): IPAH 12 +/- 2, controls 6 +/- 0.9; P = 0.04]. HA levels were also higher in IPAH PASMC lysates. The increased HA was biologically relevant as shown by tissue staining and increased HA-specific binding of mononuclear cells to IPAH compared with control PASMCs [number of bound cells x 10(4) (mean +/- SD): IPAH 9.5 +/- 3, control 3.0 +/- 1; P = 0.01]. This binding was abrogated by the addition of hyaluronidase. HA synthase-2 and hyaluronidase-2 were predominant in control and IPAH PASMCs. Interestingly, the expressions of HA synthase-2 and hyaluronidase-2 were approximately 2-fold lower in IPAH compared with controls [HA synthase-2 (relative expression mean +/- SE): IPAH 4.3 +/- 0.02, control 7.8 +/- 0.1; P = 0.0004; hyaluronidase-2 (relative expression mean +/- SE): IPAH 4.2 +/- 0.06, control 7.6 +/- 0.07; P = 0.008]. Thus patients with IPAH have higher circulating levels of HA, and PASMCs derived from IPAH lungs produce more HA compared with controls. This is associated with increased tissue levels and increased binding of inflammatory cells suggesting a role for HA in remodeling and inflammation in IPAH.
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Registered trials
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