Dataset related to the article: "In vivo evidence supports the effectiveness of the longevity-associated protein LAV-BPIFB4 in reducing adipose tissue-derived mediators of systemic inflammation to prevent vascular insult and atheromatous change"

ABSTRACT Obesity triggers chronic low-grade inflammation contributing to cardiovascular and meta-bolic diseases. Over-release of adipokines and pro-inflammatory mediators by white adiposetissue (WAT) enhances inflammation through a feedforward loop involving endothelial andimmune cells, promoting atherosclerosis. Our previous studies showed that in vivo genetransfer of the longevity-associated variant (LAV) of BPIFB4 restores endothelial and cardiacfunction and reduces systemic inflammation in mouse models. Here we investigated theanti-inflammatory potential of orally administered recombinant rhLAV-BPIFB4 in ApoE-/-mice fed a high-fat diet to elucidate its role in modulating endothelial dysfunction primed byadipose tissue inflammation. We studied n = 5 ApoE-/- mice on standard diet (SD), n = 5(VEH-HFD) and n = 6 (LAV-HFD) ApoE-/- mice fed high-fat diet without or with rhLAV-BPIFB4protein. Primary pre-adipocyte cultures were established from epididymal WAT to evaluateCD45+CD38+ leukocyte infiltration, inflammatory profile of pre-adipocytes, and ex vivoeffects of conditioned media on vessels. Oral administration of rhLAV-BPIFB4 in ApoE-/-mice fed high-fat diet dampens atherosclerosis by preserving endothelial integrity andreducing ICAM+ and CD68+ cell infiltration. Despite unchanged adiposity, systemicallyrhLAV-BPIFB4 reduces pro-inflammatory cytokines (IL-1α/β, TNF-α, IL-6) while mildly increas-ing IL-10 levels. Supernatants from pre-adipocytes treated with rhLAV-BPIFB4 demonstratesimilar anti-inflammatory cytokine profiles. Conditioned media from rhLAV-treated eWAT exvivo restores endothelial function in dysfunctional arteries (VEH-HFD vs LAV-HFD, ***p <0.001). Collectively our data show that targeting adipocyte-associated inflammation, LAV-BPIFB4 emerges as a promising therapeutic strategy to counteract endothelial dysfunction inobesity.