ArticleCirculation2013
Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension.
Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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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
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2018Guideline
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Paradigm shift: from pulmonary vasodilation to cardiopulmonary dual-track therapy-a comprehensive review of pathophysiology and advances in pulmonary hypertension-associated right heart failure.Respiratory research · 2026Review
- Aldosterone increases the expression and subcellular localization of SERCA2a and SERCA2b in the rat mesenteric artery.Frontiers in physiology · 2026Article
- A highly mobile adeno-associated virus targeting vascular smooth muscle cells for the treatment of pulmonary arterial hypertension.Nature biomedical engineering · 2025Article
- Pulmonary hypertension.Nature reviews. Disease primers · 2024Review
- Metabolic gene therapy in a canine with pulmonary hypertension secondary to degenerative mitral valve disease.Frontiers in veterinary science · 2024Article
- Acquired disorders of mitochondrial metabolism and dynamics in pulmonary arterial hypertension.Frontiers in cell and developmental biology · 2023Review
- miRNA Pathway Alteration in Response to Non-Coding RNA Delivery in Viral Vector-Based Gene Therapy.International journal of molecular sciences · 2022Review
- Cross-bridge thermodynamics in pulmonary arterial hypertensive right-ventricular failure.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1Acta pharmaceutica Sinica. B · 2022Article
- Endobronchial Aerosolized AAV1.SERCA2a Gene Therapy in a Pulmonary Hypertension Pig Model: Addressing the Lung Delivery Bottleneck.Human gene therapy · 2022Article
- Review
- Notch4 mediates vascular remodeling via ERK/JNK/P38 MAPK signaling pathways in hypoxic pulmonary hypertension.Respiratory research · 2022Article
- TRB3 mediates vascular remodeling by activating the MAPK signaling pathway in hypoxic pulmonary hypertension.Respiratory research · 2021Article
- Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Article
- Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension.Circulation · 2021Article
- Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.Circulation. Heart failure · 2021Review
- C1q/TNF-related protein-9 ameliorates hypoxia-induced pulmonary hypertension by regulating secretion of endothelin-1 and nitric oxide mediated by AMPK in rats.Scientific reports · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPulmonary arterial hypertension (PAH) is characterized by dysregulated proliferation of pulmonary artery smooth muscle cells leading to (mal)adaptive vascular remodeling. In the systemic circulation, vascular injury is associated with downregulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) and alterations in Ca(2+) homeostasis in vascular smooth muscle cells that stimulate proliferation. We, therefore, hypothesized that downregulation of SERCA2a is permissive for pulmonary vascular remodeling and the development of PAH. METHODS AND
resultsSERCA2a expression was decreased significantly in remodeled pulmonary arteries from patients with PAH and the rat monocrotaline model of PAH in comparison with controls. In human pulmonary artery smooth muscle cells in vitro, SERCA2a overexpression by gene transfer decreased proliferation and migration significantly by inhibiting NFAT/STAT3. Overexpresion of SERCA2a in human pulmonary artery endothelial cells in vitro increased endothelial nitric oxide synthase expression and activation. In monocrotaline rats with established PAH, gene transfer of SERCA2a via intratracheal delivery of aerosolized adeno-associated virus serotype 1 (AAV1) carrying the human SERCA2a gene (AAV1.SERCA2a) decreased pulmonary artery pressure, vascular remodeling, right ventricular hypertrophy, and fibrosis in comparison with monocrotaline-PAH rats treated with a control AAV1 carrying β-galactosidase or saline. In a prevention protocol, aerosolized AAV1.SERCA2a delivered at the time of monocrotaline administration limited adverse hemodynamic profiles and indices of pulmonary and cardiac remodeling in comparison with rats administered AAV1 carrying β-galactosidase or saline.
conclusionsDownregulation of SERCA2a plays a critical role in modulating the vascular and right ventricular pathophenotype associated with PAH. Selective pulmonary SERCA2a gene transfer may offer benefit as a therapeutic intervention in PAH.
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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.