Since its discovery, there has been some interest in the longevity-associated variant of human BPIFB4. It appears to reduce inflammation and improve function in the aging heart, reducing the incidence and impact of heart disease. Of particular interest is that it improves capillary density in heart tissue; recall that capillary density declines with age. Researchers are now working towards gene therapies and protein therapies that deliver the variant BPIFB4 as a way to treat forms of cardiomyopathy in the aged heart. Interestingly it appears that this protein can be delivered orally, which is quite unusual, and no doubt one of the reasons why there is greater interest in this approach versus others.
Aging is influenced by genetic determinants and comorbidities, among which diabetes increases the risk for heart failure with preserved ejection fraction. There is no therapy to prevent heart dysfunction in aging and diabetic individuals. In previous studies, a single administration of the longevity-associated variant (LAV) of the human BPIFB4 gene halted heart decline in older and type 2 diabetic mice. Here, we asked whether orally administered LAV-BPIFB4 protein replicates these benefits.
Proteins are effective biotherapeutics and have several advantages over gene therapy, especially for prolonged treatments. In the present study, we investigated the possibility that the LAV-BPIFB4 protein protects cardiac health in older and obese mice with type 2 diabetes. Results show that LAV-BPIFB4 therapy can benefit both conditions, indicating that this longevity-associated protein can antagonize two prevalent risk factors for heart failure. In aging mice, LAV-BPIFB4 increased myocardial Bpifb4 expression, improving heart contractility and capillarity while reducing perivascular fibrosis and senesce. In male diabetic mice, LAV-BPIFB4 therapy improved systolic function, microvascular density, and senescence, whereas the benefit was limited to systolic function in females.
Link: https://doi.org/10.1186/s12933-024-02487-6
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