The Role of BPIFB4 in Immune System and Cardiovascular Disease: The Lesson from Centenarians.
Journal
Translational medicine @ UniSa
ISSN: 2239-9747
Titre abrégé: Transl Med UniSa
Pays: Italy
ID NLM: 101588308
Informations de publication
Date de publication:
2021
2021
Historique:
received:
16
11
2021
revised:
16
12
2021
accepted:
28
12
2021
entrez:
30
11
2022
pubmed:
1
12
2022
medline:
1
12
2022
Statut:
epublish
Résumé
Recent discoveries have shed light on the participation of the immune system in the physio pathology of the cardiovascular system underpinning the importance of keeping the balance of the first to preserve the latter. Aging, along with other risk factors, can challenge such balance triggering the onset of cardiovascular diseases. Among several mediators ensuring the proper cross-talk between the two systems, bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been shown to have a pivotal role, also by sustaining important signals such as eNOS and PKC-alpha. In addition, the Longevity-associated variant (LAV), which is an haplotype allele in BPIFB4 characterized by 4 missense polymorphisms, enriched in homozygosity in Long Living Individuals (LLIs), has been shown to be efficient, if administered systemically through gene therapy, in improving many aspects of cardiovascular diseases (CVDs). This occurs mainly through a fine immune system remodeling across: 1) a M2 macrophage polarizing effect, 2) a favorable redistribution of the circulating monocyte cell subsets and 3) the reduction of T-cell activation. Furthermore, LAV-BPIFB4 treatment induced a desirable recovery of the inflammatory balance by mitigating the pro-inflammatory factor levels and enhancing the anti-inflammatory boost through a mechanism that is partially dependent on SDF-1/CXCR4 axis. Importantly, the remarkable effects of LAV-BPIFB4 treatment, which translates in increased BPIFB4 circulating levels, mirror what occurs in long-living individuals (LLIs) in whom the high circulating levels of BPIFB4 are protective from age-related and CVDs and emphasize the reason why LLIs are considered a model of successful aging. Here, we review the mechanisms by which LAV-BPIFB4 exerts its immunomodulatory activity in improving the cardiovascular-immune system dialogue that might strengthen its role as a key mediator in CVDs.
Identifiants
pubmed: 36447743
doi: 10.37825/2239-9754.1029
pii: tmed-24-01-001
pmc: PMC9673912
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1-12Informations de copyright
© 2021 Università di Salerno.
Déclaration de conflit d'intérêts
Conflict of interest All authors declare no financial or competing interests that are directly relevant to the content of this manuscript.
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