ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
SERCA2a gene transfer enhances eNOS expression and activity in endothelial cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Protective effect of SERCA2a-SUMOylation by SUMO-1 on diabetes-induced atherosclerosis and aortic vascular injury.Molecular and cellular biochemistry · 2025Article
- AAV delivery strategy with mechanical support for safe and efficacious cardiac gene transfer in swine.Nature communications · 2024Article
- Rap1A Modulates Store-Operated Calcium Entry in the Lung Endothelium: A Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Article
- Gene Therapy for Cardiovascular Disease: Clinical Perspectives.Yonsei medical journal · 2024Review
- Review
- Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension.Circulation · 2021Article
- Attenuation of the upregulation of NF‑κB and AP‑1 DNA‑binding activities induced by tunicamycin or hypoxia/reoxygenation in neonatal rat cardiomyocytes by SERCA2a overexpression.International journal of molecular medicine · 2021Article
- The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells.Comprehensive Physiology · 2021Article
- Intracoronary Sarcoplasmic Reticulum Calcium-ATPase Gene Therapy in Advanced Heart Failure Patients with reduced Ejection Fraction: A Prospective Cohort Study.Clinics (Sao Paulo, Brazil) · 2020Article
- Correcting Calcium Dysregulation in Chronic Heart Failure Using SERCA2a Gene Therapy.International journal of molecular sciences · 2018Review
- Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases.Heart failure reviews · 2017Review
- Use of Adeno-Associated Virus Vector for Cardiac Gene Delivery in Large-Animal Surgical Models of Heart Failure.Human gene therapy. Clinical development · 2017Review
- The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis.Scientific reports · 2016Article
- Gene therapy for the treatment of heart failure: promise postponed.European heart journal · 2016Review
- Intratracheal Gene Delivery of SERCA2a Ameliorates Chronic Post-Capillary Pulmonary Hypertension: A Large Animal Model.Journal of the American College of Cardiology · 2016Article
- Post-translational Modifications in Heart Failure: Small Changes, Big Impact.Heart, lung & circulation · 2016Review
- Small Molecular Allosteric Activator of the Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Attenuates Diabetes and Metabolic Disorders.The Journal of biological chemistry · 2016Article
- A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells.PloS one · 2016Article
- Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.Cardiovascular research · 2015Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Congestive heart failure (HF) is associated with impaired endothelium-dependent nitric oxide-mediated vasodilatation. The aim of this study was to examine the effects of sarco/endoplasmic reticulum (ER) Ca(2+)-ATPase 2a (SERCA2a) gene transfer on endothelial function in a swine HF model. Two months after the creation of mitral regurgitation to induce HF, the animals underwent intracoronary injection of adeno-associated virus (AAV) carrying SERCA2a (n = 7) or saline (n = 6). At 4 months, coronary flow (CF) was measured in the mid-portion of the left anterior descending (LAD) artery. In the failing animals, CF was decreased significantly; SERCA2a gene transfer rescued CF to levels observed in sham-group [ml/min/g, 0.47 +/- 0.064 saline versus 0.89 +/- 0.116, SERCA2a; P < 0.05; 1.00 +/- 0. 185 sham P = NS (nonsignificant)]. In coronary arteries from HF animals, SERCA2a and endothelial isoform of nitric oxide synthase (eNOS) protein expression were decreased, but restored to normal levels by SERCA2a gene transfer. In human coronary artery endothelial cells (HCAECs), SERCA2a overexpression increased eNOS expression, phosphorylation, eNOS promoter activity, Ca(2+) storage capacity, and enhanced histamine-induced calcium oscillations, eNOS activity, and cyclic guanosine monophosphate (cGMP) production. Thus, SERCA2a gene transfer increases eNOS expression and activity by modulating calcium homeostasis to improve CF. These findings suggest that SERCA2a gene transfer improves vascular reactivity in the setting of HF.
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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.