ArticleMolecular genetics and metabolism2010
Upregulation of elastase activity in aorta in mucopolysaccharidosis I and VII dogs may be due to increased cytokine expression.
Article in Molecular genetics and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Combining angiotensin receptor blockade and enzyme replacement therapy for vascular disease in mucopolysaccharidosis type I.Molecular genetics and metabolism reports · 2024Article
- The Interplay of Glycosaminoglycans and Cysteine Cathepsins in Mucopolysaccharidosis.Biomedicines · 2023Review
- Mucopolysaccharidosis Type IVA: Extracellular Matrix Biomarkers in Cardiovascular Disease.Frontiers in cardiovascular medicine · 2022Article
- Lysosome Function in Cardiovascular Diseases.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Review
- Network Analysis Reveals Proteins Associated with Aortic Dilatation in Mucopolysaccharidoses.Interdisciplinary sciences, computational life sciences · 2021Article
- Aortic Root Dilatation in Taiwanese Patients with Mucopolysaccharidoses and the Long-Term Effects of Enzyme Replacement Therapy.Diagnostics (Basel, Switzerland) · 2020Article
- Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation.JCI insight · 2020Article
- Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy.Cells · 2020Review
- Abnormally increased carotid intima media-thickness and elasticity in patients with Morquio A disease.Orphanet journal of rare diseases · 2020Article
- Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms.Journal of clinical medicine · 2020Article
- Aortopathies in mouse models of Pompe, Fabry and Mucopolysaccharidosis IIIB lysosomal storage diseases.PloS one · 2020Article
- Effects of gene therapy on cardiovascular symptoms of lysosomal storage diseases.Genetics and molecular biology · 2019Article
- Cardiovascular Histopathology of a 11-Year Old with Mucopolysaccharidosis VII Demonstrates Fibrosis, Macrophage Infiltration, and Arterial Luminal Stenosis.JIMD reports · 2018Article
- Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies .The Yale journal of biology and medicine · 2017Review
- Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery of Sleeping Beauty Transposons: Implications for Non-Viral Gene Therapy of Systemic Disease.Human gene therapy · 2017Article
- The Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls.International journal of molecular sciences · 2017Article
- Aortic Root Dilatation in Mucopolysaccharidosis I-VII.International journal of molecular sciences · 2016Article
- Neonatal cellular and gene therapies for mucopolysaccharidoses: the earlier the better?Journal of inherited metabolic disease · 2016Review
- Immune-Mediated Inflammation May Contribute to the Pathogenesis of Cardiovascular Disease in Mucopolysaccharidosis Type I.PloS one · 2016Article
- A review of gene therapy in canine and feline models of lysosomal storage disorders.Human gene therapy. Clinical development · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mucopolysaccharidosis I (MPS I) and MPS VII are due to loss-of-function mutations within the genes that encode the lysosomal enzymes alpha-l-iduronidase and beta-glucuronidase, respectively, and result in accumulation of glycosaminoglycans and multisystemic disease. Both disorders are associated with elastin fragmentation and dilatation of the aorta. Here, the pathogenesis and effect of gene therapy on aortic disease in canine models of MPS was evaluated. We found that cathepsin S is upregulated at the mRNA and enzyme activity level, while matrix metalloproteinase 12 (MMP-12) is upregulated at the mRNA level, in aortas from untreated MPS I and MPS VII dogs. Both of these proteases can degrade elastin. In addition, mRNA levels for the interleukin 6-like cytokine oncostatin M were increased in MPS I and MPS VII dog aortas, while mRNA for tumor necrosis factor alpha and toll-like receptor 4 were increased in MPS VII dog aortas. These cytokines could contribute to upregulation of the elastases. Neonatal intravenous injection of a retroviral vector expressing beta-glucuronidase to MPS VII dogs reduced RNA levels of cathepsin S and MMP-12 and aortic dilatation was delayed, albeit dilatation developed at late times after gene therapy. A post-mortem aorta from a patient with MPS VII also exhibited elastin fragmentation. We conclude that aortic dilatation in MPS I and MPS VII dogs is likely due to degradation of elastin by cathepsin S and/or MMP-12. Inhibitors of these enzymes or these cytokine-induced signal transduction pathways might reduce aortic disease in patients with MPS.
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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.