Effects of apelin on age-associated neovascularization impairment in peripheral artery disease

Abstract

Aims

Peripheral artery disease (PAD) is a prevalent vascular condition in the elderly. Aging induces senescence and dysfunction of endothelial cells (ECs), which contributes to impaired neovascularization. This study aims to investigate the therapeutic potential of apelin in restoring neovascularization in older patients with PAD.

Materials and methods

We measured plasma apelin levels of young and elderly patients with PAD, as well as in mice following hindlimb ischemia (HLI). Aged mice were treated with apelin or vehicle. Blood flow recovery was monitored using Laser Doppler imaging. To evaluate neovascularization, we performed micro-CT-based vascular angiography, whole-mount, and immunofluorescence staining. In addition, the effects of apelin on ECs were assessed by measuring reactive oxygen species, senescence-associated β-galactosidase staining, and performing a series of functional assays.

Key findings

Here, we report for the first time that plasma apelin levels are significantly reduced in older PAD patients and are closely associated with relevant clinical parameters. A similar reduction was also observed in mice following HLI. In aged mice with HLI, apelin treatment markedly enhanced blood flow recovery. Further analysis demonstrated that apelin promotes neovascularization after ischemia. Both in vivo and in vitro experiments confirmed that apelin facilitates neovascularization by improving endothelial function and mitigating ECs senescence via activation of APJ.

Significance

This study integrates clinical observations with experimental evidence, highlighting the therapeutic potential of apelin in promoting neovascularization and enhancing its translational relevance for the treatment of PAD in the elderly.