ArticleEuropean journal of heart failure2020
Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signalling pathway.
Article in European journal of heart failure, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Artificial intelligence-assisted reinterpretation of preclinical progeria research suggests a hierarchical nuclear-vascular resilience framework with translational implications.International journal of biological sciences · 2026Article
- Gene- and cell-based therapy in cardiovascular diseases.Journal of cardiovascular pharmacology · 2025Article
- Review
- The longevity-associated BPIFB4 gene guarantees vascular homeostasis and immune protection through platelets.GeroScience · 2024Article
- Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction.Cardiovascular diabetology · 2024Article
- Mechanistic correlation of molecular pathways in obesity-mediated stroke pathogenesis.Pharmacological reports : PR · 2024Review
- The tyrosine kinase inhibitor Dasatinib reduces cardiac steatosis and fibrosis in obese, type 2 diabetic mice.Cardiovascular diabetology · 2023Article
- BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice.Cell death & disease · 2023Article
- The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy.Cardiovascular research · 2023Article
- Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice.International journal of molecular sciences · 2023Article
- Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.Medicina (Kaunas, Lithuania) · 2023Article
- Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease.International journal of molecular sciences · 2022Article
- Molecular explanation of Wnt/βcatenin antagonist pyrvinium mediated calcium equilibrium changes in aging cardiovascular disorders.Molecular biology reports · 2022Review
- Gender Differences Associated with the Prognostic Value of BPIFB4 in COVID-19 Patients: A Single-Center Preliminary Study.Journal of personalized medicine · 2022Article
- Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38Cell death & disease · 2022Article
- Article
- Accelerated Cardiac Aging in Patients With Congenital Heart Disease.Frontiers in cardiovascular medicine · 2022Review
- BPIFB4 Circulating Levels and Its Prognostic Relevance in COVID-19.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.Clinical science (London, England : 1979) · 2021Review
- Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept.Frontiers in immunology · 2021Article
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18 authors at 7 institutions in 2 countries.
Funding
Abstract
aimsHomozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. METHODS AND
resultsCompared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild-type-BPIFB4 exerted no benefit. Interestingly, LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and up-regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 up-regulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor.
conclusionsIn mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease.
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