ArticleJournal of the American College of Cardiology2015
Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.
Article in Journal of the American College of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 85 citations in OpenAlex.
- Cold and hot fibrosis define clinically distinct cardiac pathologies.Cell systems · 2025Article
- Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection.International journal of drug discovery and pharmacology · 2024Article
- Synthetic biology approach revealed enhancement in haeme oxygenase-1 gene expression by codon pair optimization while reduction by codon deoptimization.Annals of medicine and surgery (2012) · 2024Article
- Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.Frontiers in immunology · 2024Review
- An ischemic area-targeting, peroxynitrite-responsive, biomimetic carbon monoxide nanogenerator for preventing myocardial ischemia-reperfusion injury.Bioactive materials · 2023Article
- MicroRNAs as therapeutic targets in cardiovascular disease.The Journal of clinical investigation · 2022Review
- Gut Bacterial Composition and Functional Potential of Tibetan Pigs Under Semi-Grazing.Frontiers in microbiology · 2022Article
- Review
- Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.Clinical science (London, England : 1979) · 2021Review
- Biologics and their delivery systems: Trends in myocardial infarction.Advanced drug delivery reviews · 2021Review
- Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway.Stem cells international · 2021Article
- Variability in Cardiac miRNA-122 Level Determines Therapeutic Potential of miRNA-Regulated AAV Vectors.Molecular therapy. Methods & clinical development · 2020Article
- Heme Oxygenase-1 Upregulation: A Novel Approach in the Treatment of Cardiovascular Disease.Antioxidants & redox signaling · 2020Review
- Identification of potential molecular mechanisms and small molecule drugs in myocardial ischemia/reperfusion injury.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Evaluating Novel Targets of Ischemia Reperfusion Injury in Pig Models.International journal of molecular sciences · 2019Review
- Analysis of recombinant adeno-associated viral vector shedding in sheep following intracoronary delivery.Gene therapy · 2019Article
- Targeting Heme Oxygenase-1 in Cardiovascular and Kidney Disease.Antioxidants (Basel, Switzerland) · 2019Review
- Phikud Navakot Modulates the Level of Pro-Inflammatory Mediators and the Protein Expression of SOD1 and 2 and the Nrf2/HO-1 Signaling Pathway in Rats with Acute Myocardial Infarction.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Translational Aspects of Adeno-Associated Virus-Mediated Cardiac Gene Therapy.Human gene therapy · 2018Review
- Human Cardiac Gene Therapy.Circulation research · 2018Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHeme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear.
objectivesThis study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model.
methodsMurine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed.
resultsHuman microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals.
conclusionsWhereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model.
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