ArticleHuman gene therapy2013
Intravenous adeno-associated virus serotype 8 encoding urocortin-2 provides sustained augmentation of left ventricular function in mice.
Article in Human gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 19 citations in OpenAlex.
- Effects ofHuman gene therapy · 2023Article
- Article
- Article
- Urocortin 2 Gene Transfer Improves Heart Function in Aged Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Cardiac-Directed Expression of Adenylyl Cyclase Catalytic Domain (Human gene therapy · 2019Article
- Urocortin 2 Gene Transfer Reduces the Adverse Effects of a Western Diet on Cardiac Function in Mice.Human gene therapy · 2019Article
- Significant alteration of liver metabolites by AAV8.Urocortin 2 gene transfer in mice with insulin resistance.PloS one · 2019Article
- Urocortin 3 Gene Transfer Increases Function of the Failing Murine Heart.Human gene therapy · 2019Article
- Effects of Urocortin 2 Versus Urocortin 3 Gene Transfer on Left Ventricular Function and Glucose Disposal.JACC. Basic to translational science · 2018Article
- Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction.The Journal of experimental medicine · 2017Article
- Cardiac-Directed Expression of Adenylyl Cyclase Catalytic Domain Reverses Cardiac Dysfunction Caused by Sustained Beta-Adrenergic Receptor Stimulation.JACC. Basic to translational science · 2016Article
- One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance.JCI insight · 2016Article
- Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.Cardiovascular research · 2015Review
- Comparative effects of urocortins and stresscopin on cardiac myocyte contractility.Journal of molecular and cellular cardiology · 2015Article
- Intravenous AAV8 Encoding Urocortin-2 Increases Function of the Failing Heart in Mice.Human gene therapy · 2015Article
- The potential of adeno-associated viral vectors for gene delivery to muscle tissue.Expert opinion on drug delivery · 2014Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Urocortin-2 (UCn2) peptide infusion increases cardiac function in patients with heart failure, but chronic peptide infusion is cumbersome, costly, and provides only short-term benefits. Gene transfer would circumvent these shortcomings. Here we ask whether a single intravenous injection of adeno-associated virus type 8 encoding murine urocortin-2 (AAV8.UCn2) could provide long-term elevation in plasma UCn2 levels and increased left ventricular (LV) function. Normal mice received AAV8.UCn2 (5×10¹¹ genome copies, intravenous). Plasma UCn2 increased 15-fold 6 weeks and >11-fold 7 months after delivery. AAV8 DNA and UCn2 mRNA expression was persistent in LV and liver up to 7 months after a single intravenous injection of AAV8.UCn2. Physiological studies conducted both in situ and ex vivo showed increases in LV +dP/dt and in LV -dP/dt, findings that endured unchanged for 7 months. SERCA2a mRNA and protein expression was increased in LV samples and Ca²⁺ transient studies showed an increased rate of Ca²⁺ decline in cardiac myocytes from mice that had received UCn2 gene transfer. We conclude that a single intravenous injection of AAV8.UCn2 increases plasma UCn2 and increases LV systolic and diastolic function for at least 7 months. The simplicity of intravenous injection of a long-term expression vector encoding a gene with paracrine activity to increase cardiac function is a potentially attractive strategy in clinical settings. Future studies will determine the usefulness of this approach in the treatment of heart failure.
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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.