<i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs
2025
Aoqi Xiang | Hua Guan | Peihong Su | Lusha Zhang | Xiaochang Chen | Qi Yu
Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that <i>IGFBP5</i> is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of <i>IGFBP5</i> in atherosclerosis. The expression of <i>IGFBP5</i> was induced in the skeletal muscle of male ApoE<sup>−/−</sup> mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating <i>IGFBP5</i> levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of <i>IGFBP5</i> function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that <i>IGFBP5</i> overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened <i>IGFBP5</i> levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of <i>IGFBP5</i> on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. <i>IGFBP5</i> promotes atherosclerosis in ApoE<sup>−/−</sup> mice through the phenotypic transformation of VSMCs. This finding suggests that <i>IGFBP5</i> has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future.
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