• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

BPIFB4 及其与长寿相关的单倍型可保护人类和小鼠免受心肌缺血的影响。

BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice.

机构信息

Cardiovascular Department, IRCCS MultiMedica, Milan, Italy.

Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy.

出版信息

Cell Death Dis. 2023 Aug 15;14(8):523. doi: 10.1038/s41419-023-06011-8.

DOI:10.1038/s41419-023-06011-8
PMID:37582912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10427721/
Abstract

Long-living individuals (LLIs) escape age-related cardiovascular complications until the very last stage of life. Previous studies have shown that a Longevity-Associated Variant (LAV) of the BPI Fold Containing Family B Member 4 (BPIFB4) gene correlates with an extraordinarily prolonged life span. Moreover, delivery of the LAV-BPIFB4 gene exerted therapeutic action in murine models of atherosclerosis, limb ischemia, diabetic cardiomyopathy, and aging. We hypothesize that downregulation of BPIFB4 expression marks the severity of coronary artery disease (CAD) in human subjects, and supplementation of the LAV-BPIFB4 protects the heart from ischemia. In an elderly cohort with acute myocardial infarction (MI), patients with three-vessel CAD were characterized by lower levels of the natural logarithm (Ln) of peripheral blood BPIFB4 (p = 0.0077). The inverse association between Ln BPIFB4 and three-vessel CAD was confirmed by logistic regression adjusting for confounders (Odds Ratio = 0.81, p = 0.0054). Moreover, in infarcted mice, a single administration of LAV-BPIFB4 rescued cardiac function and vascularization. In vitro studies showed that LAV-BPIFB4 protein supplementation exerted chronotropic and inotropic actions on induced pluripotent stem cell (iPSC)-derived cardiomyocytes. In addition, LAV-BPIFB4 inhibited the pro-fibrotic phenotype in human cardiac fibroblasts. These findings provide a strong rationale and proof of concept evidence for treating CAD with the longevity BPIFB4 gene/protein.

摘要

长寿个体（LLI）直到生命的最后阶段才会逃脱与年龄相关的心血管并发症。先前的研究表明，BPI 折叠包含家族 B 成员 4（BPIFB4）基因的长寿相关变体（LAV）与异常延长的寿命相关。此外，LAV-BPIFB4 基因的传递在动脉粥样硬化、肢体缺血、糖尿病心肌病和衰老的小鼠模型中发挥了治疗作用。我们假设 BPIFB4 表达的下调标志着人类受试者冠状动脉疾病（CAD）的严重程度，并且 LAV-BPIFB4 的补充可保护心脏免受缺血。在急性心肌梗死（MI）的老年队列中，三支血管 CAD 患者的外周血 BPIFB4 的自然对数（Ln）水平较低（p=0.0077）。通过调整混杂因素的逻辑回归证实了 Ln BPIFB4 与三支血管 CAD 之间的反比关系（Odds Ratio=0.81，p=0.0054）。此外，在梗死小鼠中，单次给予 LAV-BPIFB4 可挽救心脏功能和血管生成。体外研究表明，LAV-BPIFB4 蛋白补充对诱导多能干细胞（iPSC）衍生的心肌细胞具有变时和变力作用。此外，LAV-BPIFB4 抑制了人心脏成纤维细胞的促纤维化表型。这些发现为用长寿 BPIFB4 基因/蛋白治疗 CAD 提供了强有力的理由和概念验证证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/6500d906c136/41419_2023_6011_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/cbed884b7c42/41419_2023_6011_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/82e08c3e1ac6/41419_2023_6011_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/6500d906c136/41419_2023_6011_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/cbed884b7c42/41419_2023_6011_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/82e08c3e1ac6/41419_2023_6011_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8182/10427721/6500d906c136/41419_2023_6011_Fig3_HTML.jpg

相似文献

1
BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice.BPIFB4 及其与长寿相关的单倍型可保护人类和小鼠免受心肌缺血的影响。
Cell Death Dis. 2023 Aug 15;14(8):523. doi: 10.1038/s41419-023-06011-8.
2
The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy.与长寿相关的 BPIFB4 基因支持衰老性心肌病中的心脏功能和血管生成。
Cardiovasc Res. 2023 Jul 4;119(7):1583-1595. doi: 10.1093/cvr/cvad008.
3
Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38 macrophages and NAD decline.BPIFB4 基因长寿相关变异的转移通过减少 CD38 巨噬细胞和 NAD 下降来恢复免疫系统和血管。
Cell Death Dis. 2022 Jan 27;13(1):86. doi: 10.1038/s41419-022-04535-z.
4
Circulating BPIFB4 Levels Associate With and Influence the Abundance of Reparative Monocytes and Macrophages in Long Living Individuals.循环 BPIFB4 水平与长寿个体中修复性单核细胞和巨噬细胞的丰度相关，并影响其丰度。
Front Immunol. 2020 May 29;11:1034. doi: 10.3389/fimmu.2020.01034. eCollection 2020.
5
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.携带与人长寿相关基因变异的人类细胞，通过诱导 SDF-1/CXCR4 信号通路，改善肥胖 2 型糖尿病小鼠的心脏功能。
Eur J Heart Fail. 2020 Sep;22(9):1568-1581. doi: 10.1002/ejhf.1840. Epub 2020 May 8.
6
LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice.LAV-BPIFB4与人类虚弱程度降低相关，其转移可防止老年小鼠的虚弱进展。
Aging (Albany NY). 2019 Aug 28;11(16):6555-6568. doi: 10.18632/aging.102209.
7
The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease.与长寿相关的 BPIFB4 变体改善了 CXCR4 介导的纹状体-小胶质细胞串扰，从而防止亨廷顿病小鼠模型的疾病进展。
Cell Death Dis. 2020 Jul 18;11(7):546. doi: 10.1038/s41419-020-02754-w.
8
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.单次系统性转移与人长寿相关的基因通过 CXCR4 介导的机制可阻止 ApoE 基因敲除小鼠动脉粥样硬化和炎症的进展。
Eur Heart J. 2020 Jul 7;41(26):2487-2497. doi: 10.1093/eurheartj/ehz459.
9
The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy.在意大利奇伦托地区的长寿个体中，BPIFB4和CXCR4的表达与持续健康相关。
Aging (Albany NY). 2017 Jan 22;9(2):370-380. doi: 10.18632/aging.101159.
10
Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis.基因分析揭示一种与长寿相关的蛋白质可调节内皮功能和血管生成。
Circ Res. 2015 Jul 31;117(4):333-45. doi: 10.1161/CIRCRESAHA.117.305875. Epub 2015 Jun 1.

引用本文的文献

1
Overexpression of BPIFB4 Alleviates COPD Inflammatory Damage by Inhibiting M1 Macrophage Activation via the PI3K/AKT Pathway.BPIFB4的过表达通过PI3K/AKT途径抑制M1巨噬细胞活化减轻慢性阻塞性肺疾病的炎症损伤。
Lung. 2025 Jun 16;203(1):69. doi: 10.1007/s00408-025-00824-4.
2
The Genetic and Epigenetic Arms of Human Ageing and Longevity.人类衰老与长寿的遗传及表观遗传因素
Biology (Basel). 2025 Jan 18;14(1):92. doi: 10.3390/biology14010092.
3
Longevity-associated BPIFB4 gene counteracts the inflammatory signaling.与长寿相关的BPIFB4基因可对抗炎症信号传导。

本文引用的文献

1
The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy.与长寿相关的 BPIFB4 基因支持衰老性心肌病中的心脏功能和血管生成。
Cardiovasc Res. 2023 Jul 4;119(7):1583-1595. doi: 10.1093/cvr/cvad008.
2
Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease.BPIFB4 长寿相关变体赋予亨廷顿病 STHdh 细胞模型中的神经保护作用。
Int J Mol Sci. 2022 Dec 5;23(23):15313. doi: 10.3390/ijms232315313.
3
The Role of BPIFB4 in Immune System and Cardiovascular Disease: The Lesson from Centenarians.
Immun Ageing. 2024 Mar 12;21(1):19. doi: 10.1186/s12979-024-00424-5.
BPIFB4在免疫系统和心血管疾病中的作用：来自百岁老人的启示。
Transl Med UniSa. 2021 Dec 23;24(1):1-12. doi: 10.37825/2239-9754.1029. eCollection 2021.
4
Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38 macrophages and NAD decline.BPIFB4 基因长寿相关变异的转移通过减少 CD38 巨噬细胞和 NAD 下降来恢复免疫系统和血管。
Cell Death Dis. 2022 Jan 27;13(1):86. doi: 10.1038/s41419-022-04535-z.
5
Mechanisms of Fibroblast Activation and Myocardial Fibrosis: Lessons Learned from FB-Specific Conditional Mouse Models.成纤维细胞激活和心肌纤维化的机制：从 FB 特异性条件性小鼠模型中得到的经验教训。
Cells. 2021 Sep 14;10(9):2412. doi: 10.3390/cells10092412.
6
Soluble Receptor for Advanced Glycation End-products regulates age-associated Cardiac Fibrosis.可溶性晚期糖基化终产物受体调节与年龄相关的心脏纤维化。
Int J Biol Sci. 2021 Jun 11;17(10):2399-2416. doi: 10.7150/ijbs.56379. eCollection 2021.
7
Olfactory perception of food abundance regulates dietary restriction-mediated longevity via a brain-to-gut signal.嗅觉感知食物丰度通过脑-肠信号调节饮食限制介导的寿命延长。
Nat Aging. 2021 Mar;1(3):255-268. doi: 10.1038/s43587-021-00039-1. Epub 2021 Mar 15.
8
GRK5 is a regulator of fibroblast activation and cardiac fibrosis.GRK5 是成纤维细胞活化和心脏纤维化的调节因子。
Proc Natl Acad Sci U S A. 2021 Feb 2;118(5). doi: 10.1073/pnas.2012854118.
9
lncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease.lncRNA 表达谱及冠心病患者心外膜脂肪组织中相关 ceRNA 网络分析。
Sci Rep. 2021 Jan 15;11(1):1567. doi: 10.1038/s41598-021-81038-5.
10
GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality.GrimAge 在预测与年龄相关的临床表型和全因死亡率方面优于其他表观遗传时钟。
J Gerontol A Biol Sci Med Sci. 2021 Apr 30;76(5):741-749. doi: 10.1093/gerona/glaa286.