ArticleEuropean heart journal2020
Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism.
Article in European heart journal, 2020. 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, 68 citations in OpenAlex.
- The LAV-BPIFB4-Platelet-CD47 Axis: A Novel Mechanism Associated With Immune Resilience in Longevity.Aging cell · 2026Article
- Peripheral Blood HIST1H2AE is a Candidate Epigenetic Biomarker for Coronary Artery Disease: A Multi-Dataset Discovery and Comparative Validation Study.International journal of general medicine · 2026Article
- The cardiovascular-immune axis: crosstalk and therapy in atherosclerosis, myocarditis and vasculitis.Frontiers in immunology · 2026Review
- Article
- Cellular and molecular mechanisms underlying cardiovascular aging.Cellular & molecular biology letters · 2025Review
- BPIFB4 rs4339026 A > G polymorphism impacts COPD susceptibility in the Kashi population, China.Scientific reports · 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
- Longevity-associated BPIFB4 gene counteracts the inflammatory signaling.Immunity & ageing : I & A · 2024Article
- Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice.Cell death & disease · 2023Article
- Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice.European heart journal · 2023Article
- The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy.Cardiovascular research · 2023Article
- Bleeding risk in patients prescribed dual antiplatelet therapy and triple therapy after coronary interventions: the ADAPTT retrospective population-based cohort studies.Health technology assessment (Winchester, England) · 2023Article
- Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice.International journal of molecular sciences · 2023Article
- Comprehensive analysis of atherosclerotic plaques reveals crucial genes and molecular mechanisms associated with plaque progression and rupture.Frontiers in cardiovascular medicine · 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
- Article
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Authors and funding
30 authors at 11 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsHere, we aimed to determine the therapeutic effect of longevity-associated variant (LAV)-BPIFB4 gene therapy on atherosclerosis. METHODS AND
resultsApoE knockout mice (ApoE-/-) fed a high-fat diet were randomly allocated to receive LAV-BPIFB4, wild-type (WT)-BPIFB4, or empty vector via adeno-associated viral vector injection. The primary endpoints of the study were to assess (i) vascular reactivity and (ii) atherosclerotic disease severity, by Echo-Doppler imaging, histology and ultrastructural analysis. Moreover, we assessed the capacity of the LAV-BPIFB4 protein to shift monocyte-derived macrophages of atherosclerotic mice and patients towards an anti-inflammatory phenotype. LAV-BPIFB4 gene therapy rescued endothelial function of mesenteric and femoral arteries from ApoE-/- mice; this effect was blunted by AMD3100, a CXC chemokine receptor type 4 (CXCR4) inhibitor. LAV-BPIFB4-treated mice showed a CXCR4-mediated shift in the balance between Ly6Chigh/Ly6Clow monocytes and M2/M1 macrophages, along with decreased T cell proliferation and elevated circulating levels of interleukins IL-23 and IL-27. In vitro conditioning with LAV-BPIFB4 protein of macrophages from atherosclerotic patients resulted in a CXCR4-dependent M2 polarization phenotype. Furthermore, LAV-BPIFB4 treatment of arteries explanted from atherosclerotic patients increased the release of atheroprotective IL-33, while inhibiting the release of pro-inflammatory IL-1β, inducing endothelial nitric oxide synthase phosphorylation and restoring endothelial function. Finally, significantly lower plasma BPIFB4 was detected in patients with pathological carotid stenosis (>25%) and intima media thickness >2 mm.
conclusionTransfer of the LAV of BPIFB4 reduces the atherogenic process and skews macrophages towards an M2-resolving phenotype through modulation of CXCR4, thus opening up novel therapeutic possibilities in cardiovascular disease.
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