التفاصيل البيبلوغرافية
| العنوان: |
BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice |
| المؤلفون: |
Monica Cattaneo, Aneta Aleksova, Alberto Malovini, Elisa Avolio, Anita Thomas, Valeria Vincenza Alvino, Michael Kilcooley, Marie Pieronne-Deperrois, Antoine Ouvrard-Pascaud, Anna Maciag, Gaia Spinetti, Sophie Kussauer, Heiko Lemcke, Anna Skorska, Praveen Vasudevan, Stefania Castiglione, Angela Raucci, Robert David, Vincent Richard, Antonio Paolo Beltrami, Paolo Madeddu, Annibale Alessandro Puca |
| المصدر: |
Cell Death and Disease, Vol 14, Iss 8, Pp 1-11 (2023) |
| بيانات النشر: |
Nature Publishing Group, 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Cytology |
| مصطلحات موضوعية: |
Cytology, QH573-671 |
| الوصف: |
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. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-023-06011-8 |
| URL الوصول: |
https://doaj.org/article/348033df59064add9787c0ed75ff9450 |
| رقم الانضمام: |
edsdoj.348033df59064add9787c0ed75ff9450 |
| قاعدة البيانات: |
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