A Model of Evolutionary Selection: The Cardiovascular Protective Function of the Longevity Associated Variant of BPIFB4.
Francesco VillaAlbino CarrizzoAnna FerrarioAnna MaciagMonica CattaneoChiara Carmela SpinelliFrancesco MontellaAntonio DamatoElena CiagliaAnnibale Alessandro PucaPublished in: International journal of molecular sciences (2018)
Evolutionary forces select genetic variants that allow adaptation to environmental stresses. The genomes of centenarian populations could recapitulate the evolutionary adaptation model and reveal the secrets of disease resistance shown by these individuals. Indeed, longevity phenotype is supposed to have a genetic background able to survive or escape to age-related diseases. Among these, cardiovascular diseases (CVDs) are the most lethal and their major risk factor is aging and the associated frailty status. One example of genetic evolution revealed by the study of centenarians genome is the four missense Single Nucleotide Polymorphisms (SNPs) haplotype in bactericidal/permeability-increasing fold-containing family B, member 4 (BPIFB4) locus that is enriched in long living individuals: the longevity associated variant (LAV). Indeed, LAV-BPIFB4 is able to improve endothelial function and revascularization through the increase of endothelial nitric oxide synthase (eNOS) dependent nitric oxide production. This review recapitulates the beneficial effects of LAV-BPIFB4 and its therapeutic potential for the treatment of CVDs.
Keyphrases
- genome wide
- nitric oxide synthase
- nitric oxide
- dna methylation
- copy number
- endothelial cells
- cardiovascular disease
- drosophila melanogaster
- risk factors
- hydrogen peroxide
- intellectual disability
- gene expression
- pi k akt
- percutaneous coronary intervention
- metabolic syndrome
- acute coronary syndrome
- cell proliferation
- combination therapy
- risk assessment
- atrial fibrillation
- autism spectrum disorder
- coronary artery disease
- climate change
- cardiovascular risk factors