Older adults exhibit higher levels of VEGF-A165B, which correlates with smaller blood vessels, suggesting a connection between macrophage senescence and vascular health in aging populations.

Experiments conducted on older mice demonstrated that senescent macrophages adversely affect the healing process after hindlimb injuries in younger mice, resulting in necrosis and fibrosis.

Cellular experiments confirmed that senescent macrophages impair endothelial cell proliferation and disrupt angiogenesis pathways.

The findings suggest that targeting macrophage senescence could provide a new approach for treating arterial blockages.

Research has linked the negative effects of senescent macrophages to an increased presence of the anti-angiogenic isoform VEGF-A165B, which is detrimental to endothelial cell function.

Peripheral arterial disease (PAD) affects approximately 113 million people worldwide, presenting significant treatment challenges, particularly for older patients.

Macrophages play a crucial role in angiogenesis, but their function can decline with age, leading to impaired blood vessel formation and various health issues.

In patients with PAD, there is a notable decrease in the angiogenic isoform VEGF-A165A and a corresponding increase in VEGF-A165B, produced by macrophages.

Genetic modification of macrophages to prevent the production of VEGF-A165B mitigated their negative impact on angiogenesis, indicating a potential treatment pathway.

The study acknowledges limitations, such as not stratifying results by sex and the need to consider other inflammatory factors, while proposing future research on macrophage-targeting senolytics or anti-VEGF-A165B therapies.