ArticleThe Journal of biological chemistry2013
Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 69 citations in OpenAlex.
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- Hyaluronidase: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.Journal of human genetics · 2025Review
- Activated cardiac fibroblasts are a primary source of high-molecular-weight hyaluronan production.American journal of physiology. Cell physiology · 2025Article
- Genetic Deficiencies of Hyaluronan Degradation.Cells · 2024Review
- The Contribution of Vascular Proteoglycans to Atherothrombosis: Clinical Implications.International journal of molecular sciences · 2023Review
- Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).Journal of inflammation research · 2023Article
- The role of hyaluronan in endothelial glycocalyx and potential preventative lifestyle strategy with advancing age.Current topics in membranes · 2023Article
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- Cor Triatriatum Sinister Presenting as Cardioembolic Stroke in a Young Woman.Diagnostics (Basel, Switzerland) · 2022Article
- The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival.PLoS genetics · 2022Article
- Hyaluronan, a double-edged sword in kidney diseases.Pediatric nephrology (Berlin, Germany) · 2022Review
- Myocardial oedema: pathophysiological basis and implications for the failing heart.ESC heart failure · 2022Review
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- The cell surface hyaluronidase TMEM2 is essential for systemic hyaluronan catabolism and turnover.The Journal of biological chemistry · 2021Article
- The Association Between Plasma Hyaluronan Level and Plaque Types in ST-Segment-Elevation Myocardial Infarction Patients.Frontiers in cardiovascular medicine · 2021Article
- Hyaluronan: Metabolism and Function.Biomolecules · 2020Review
- Identification of novel genetic variants associated with short stature in a Baka Pygmies population.Human genetics · 2020Article
- Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System.International journal of molecular sciences · 2020Review
- Hyaluronidase-2 Regulates RhoA Signaling, Myofibroblast Contractility, and Other Key Profibrotic Myofibroblast Functions.The American journal of pathology · 2020Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyaluronidase (HYAL) 2 is a membrane-anchored protein that is proposed to hydrolyze hyaluronan (HA) to smaller fragments that are internalized for breakdown. Initial studies of a Hyal2 knock-out (KO) mouse revealed a mild phenotype with high serum HA, supporting a role for HYAL2 in HA breakdown. We now describe a severe cardiac phenotype, deemed acute, in 54% of Hyal2 KO mice on an outbred background; Hyal2 KO mice without the severe cardiac phenotype were designated non-acute. Histological studies of the heart revealed that the valves of all Hyal2 KO mice were expanded and the extracellular matrix was disorganized. HA was detected throughout the expanded valves, and electron microscopy confirmed that the accumulating material, presumed to be HA, was extracellular. Both acute and non-acute Hyal2 KO mice also exhibited increased HA in the interstitial extracellular matrix of atrial cardiomyocytes compared with control mice. Consistent with the changes in heart structure, upper ventricular cardiomyocytes in acute Hyal2 KO mice demonstrated significant hypertrophy compared with non-acute KO and control mice. When the lungs were examined, evidence of severe fibrosis was detected in acute Hyal2 KO mice but not in non-acute Hyal2 KO or control mice. Total serum and heart HA levels, as well as size, were increased in acute and non-acute Hyal2 KO mice compared with control mice. These findings indicate that HYAL2 is essential for the breakdown of extracellular HA. In its absence, extracellular HA accumulates and, in some cases, can lead to cardiopulmonary dysfunction. Alterations in HYAL2 function should be considered as a potential contributor to cardiac pathologies in humans.
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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.