ArticleCardiovascular research2017
LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent mechanism.
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- New Nutraceutical Combination Reduces Blood Pressure and Improves Exercise Capacity in Hypertensive Patients Via a Nitric Oxide-Dependent Mechanism.Journal of the American Heart Association · 2020Trial
- SERCA2 gatekeeper role in aortic autophagy: targeting the CaActa pharmacologica Sinica · 2026Article
- Gain-of-function PPM1D mutations attenuate ischemic stroke.Cell death and differentiation · 2025Article
- Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction.Cardiovascular diabetology · 2024Article
- 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
- Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease.International journal of molecular sciences · 2022Article
- Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38Cell death & disease · 2022Article
- BPIFB4 Circulating Levels and Its Prognostic Relevance in COVID-19.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- The Role of BPIFB4 in Immune System and Cardiovascular Disease: The Lesson from Centenarians.Translational medicine @ UniSa · 2021Article
- Flexible Mixture Model Approaches That Accommodate Footprint Size Variability for Robust Detection of Balancing Selection.Molecular biology and evolution · 2020Article
- New Insights for BPIFB4 in Cardiovascular Therapy.International journal of molecular sciences · 2020Review
- Sodium-not harmful?Pediatric nephrology (Berlin, Germany) · 2020Article
- 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.European journal of heart failure · 2020Article
- The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease.Cell death & disease · 2020Article
- 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.European heart journal · 2020Article
- Molecular therapies delaying cardiovascular aging: disease- or health-oriented approaches.Vascular biology (Bristol, England) · 2020Review
- Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy.Digestive diseases and sciences · 2019Article
- A Model of Evolutionary Selection: The Cardiovascular Protective Function of the Longevity Associated Variant of BPIFB4.International journal of molecular sciences · 2018Review
- The Impact of Aging on Cardio and Cerebrovascular Diseases.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAgeing is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in endothelial function. A genetic study on long-living individuals-who are characterized by delays in ageing and in the onset of cardiovascular disease-previously revealed I229V (rs2070325) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO production and vasorelaxation through a protein kinase R-like endoplasmic reticulum kinase/14-3-3/heat shock protein 90 signal. Here, we further characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement of vascular function. METHODS AND
resultsLAV-BPIFB4 upregulated eNOS function via mobilization of Ca2+ and activation of protein kinase C alpha (PKCα). Indeed, the overexpression of LAV-BPIFB4 in human endothelial cells enhanced ATP-induced Ca2+ mobilization and the translocation of PKCα to the plasma membrane. Coherently, pharmacological inhibition of PKCα blunted the positive effect of LAV-BPIFB4 on eNOS and endothelial function. In addition, although LAV-BPIFB4 lost the ability to activate PKCα and eNOS in ex vivo vessels studied in an external Ca2+-free medium and in vessels from eNOS-/- mice, it still potentiated endothelial activity, recruiting an alternative mechanism dependent upon endothelium-derived hyperpolarizing factor (EDHF).
conclusionsWe have identified novel molecular determinants of the beneficial effects of LAV-BPIFB4 on endothelial function, showing the roles of Ca2+ mobilization and PKCα in eNOS activation and of EDHF when eNOS is inhibited. These results highlight the role LAV-BPIFB4 can have in restoring signals that are lost during ageing.
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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.