ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Susceptibility to Cardiac Arrhythmias and Sympathetic Nerve Growth in VEGF-B Overexpressing Myocardium.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Predictive value of miR-193a-5p combined with VEGFB in the diagnosis and prognosis of CHD.Journal of cardiothoracic surgery · 2026Article
- VEGFR1 as a Target for Cardiovascular Gene Therapy.Journal of cardiovascular translational research · 2025Review
- Beneficial effects of vascular endothelial growth factor B gene transfer in the aged heart.Cardiovascular research · 2025Article
- VEGF-B is a novel mediator of ER stress which induces cardiac angiogenesis via RGD-binding integrins independent of VEGFR1/NRP activities.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Ventricular Arrhythmias and Myocardial Infarction: Electrophysiological and Neuroimmune Mechanisms.Biomedicines · 2025Review
- Sympathetic nerve signaling rewires the tumor microenvironment: a shift in "microenvironmental-ity".Cancer metastasis reviews · 2025Review
- Long-term continuous monitoring of arrhythmias in pigs with insertable cardiac monitors.Pflugers Archiv : European journal of physiology · 2024Article
- Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy.Circulation research · 2024Article
- Angiogenesis and EMT regulators in the tumor microenvironment in lung cancer and immunotherapy.Frontiers in immunology · 2024Review
- VEGF-B hypertrophy predisposes to transition from diastolic to systolic heart failure in hypertensive rats.Cardiovascular research · 2023Article
- Pathophysiological functions of semaphorins in the sympathetic nervous system.Inflammation and regeneration · 2023Review
- BMP2 gene transfer induces pericardial effusion and inflammatory response in the ischemic porcine myocardium.Frontiers in cardiovascular medicine · 2023Article
- Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision?Cells · 2022Review
- Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DGene therapy · 2022Article
- The vasculature: a therapeutic target in heart failure?Cardiovascular research · 2022Review
- Adenoviral VEGF-DFrontiers in bioengineering and biotechnology · 2022Article
- Novel Designed Proteolytically Resistant VEGF-B186R127S Promotes Angiogenesis in Mouse Heart by Recruiting Endothelial Progenitor Cells.Frontiers in bioengineering and biotechnology · 2022Article
- Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart.iScience · 2021Article
- VEGF-B Gene Therapy for the Heart: Proceed with Caution.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- The Role of Non-Coding RNAs in Controlling Cell Cycle Related Proteins in Cancer Cells.Frontiers in oncology · 2020Review
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VEGF-B gene therapy is a promising proangiogenic treatment for ischemic heart disease, but, unexpectedly, we found that high doses of VEGF-B promote ventricular arrhythmias (VAs). VEGF-B knockout, alpha myosin heavy-chain promoter (αMHC)-VEGF-B transgenic mice, and pigs transduced intramyocardially with adenoviral (Ad)VEGF- B186 were studied. Immunostaining showed a 2-fold increase in the number of nerves per field (76 vs. 39 in controls, p < 0.001) and an abnormal nerve distribution in the hypertrophic hearts of 11- to 20-month-old αMHC-VEGF-B mice. AdVEGF-B186 gene transfer (GT) led to local sprouting of nerve endings in pig myocardium (141 vs. 78 nerves per field in controls, p < 0.05). During dobutamine stress, 60% of the αMHC-VEGF-B hypertrophic mice had arrhythmias as compared to 7% in controls, and 20% of the AdVEGF-B186-transduced pigs and 100% of the combination of AdVEGF-B186- and AdsVEGFR-1-transduced pigs displayed VAs and even ventricular fibrillation. AdVEGF-B186 GT significantly increased the risk of sudden cardiac death in pigs when compared to any other GT with different VEGFs (hazard ratio, 500.5; 95% confidence interval [CI] 46.4-5,396.7; p < 0.0001). In gene expression analysis, VEGF-B induced the upregulation of Nr4a2, ATF6, and MANF in cardiomyocytes, molecules previously linked to nerve growth and differentiation. Thus, high AdVEGF-B186 overexpression induced nerve growth in the adult heart via a VEGFR-1 signaling-independent mechanism, leading to an increased risk of VA and sudden cardiac death.
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