RBM47 aggravates carotid atherosclerotic plaque instability through NEDD4L-dependent regulation of TRAF2

Atherosclerotic plaque instability is linked to dysregulated cellular stress responses and protein homeostasis within the vascular wall. RNA-binding motif protein 47 (RBM47) modulates mRNA stability and protein expression, but its contribution to the regulation of plaque stability and associated cellular injury has not been fully elucidated.

Utilizing murine and cellular models of atherosclerosis, we systematically evaluated the role of RBM47 in plaque stability-associated cellular responses. Bioinformatics analyses predicted NEDD4L and TNF receptor-associated factor 2 (TRAF2) as potential downstream targets of RBM47, implicating their possible involvement in protein homeostasis and plaque instability.

In atherosclerotic mice, reduced plaque stability was associated with enhanced cellular stress and increased RBM47 expression. Consistently, in H₂O₂-treated HA-SMCs, aggravated cellular injury coincided with marked upregulation of RBM47 and NEDD4L. The interaction between NEDD4L and TNF receptor-associated factor 2 (TRAF2) was further confirmed. Functional analyses showed that silencing RBM47 reduced NEDD4L expression, thereby attenuating NEDD4L-mediated TRAF2 ubiquitination and degradation. These molecular changes were associated with reduced cellular injury, improved plaque stability, and attenuation of atherosclerotic progression.

RBM47 enhances NEDD4L expression by stabilizing its mRNA, leading to altered TRAF2 protein homeostasis and plaque instability. These findings highlight RBM47 and its downstream signaling as potential targets for atherosclerosis intervention.