Purpose <p>Abdominal aortic aneurysm (AAA) is a progressive, age-associated vascular disorder characterized by dilation of the abdominal aorta and a high risk of rupture. RNA-binding motif protein 10 (RBM10), a key regulator of mRNA alternative splicing involved in cell cycle control and apoptosis, has not previously been investigated in AAA. This study aimed to characterize the expression and functional role of RBM10 in AAA pathogenesis.</p> Methods <p>RBM10 expression in human AAA tissues was assessed by immunofluorescence. To explore its functional relevance, genome-wide transcriptomic profiling was performed in human aortic smooth muscle cells (HASMCs) transfected with RBM10 adenovirus or negative control for 24&#xa0;h. The effects of RBM10 on HASMC proliferation and migration were evaluated using MTT and transwell assays, respectively. Apoptosis was quantified by flow cytometry.</p> Results <p>RBM10 expression was significantly elevated in human AAA tissues and in an established animal model. RBM10 overexpression markedly suppressed HASMC proliferation and migration while promoting apoptosis. Flow cytometry confirmed enhanced apoptotic rates, consistent with transcriptomic analysis demonstrating activation of the p53 pathway. Upregulation and activation of p53 were validated at the protein level.</p> Conclusions <p>These findings indicate that RBM10 contributes to AAA progression by promoting smooth muscle cell apoptosis, likely through a p53-dependent mechanism. RBM10 may represent a promising therapeutic target for preventing or slowing AAA development.</p>

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RNA-binding motif protein 10 accelerates abdominal aortic aneurysm formation by inducing smooth muscle cell apoptosis

  • Xiang-Yu Zhang,
  • Huan-Huan Chen,
  • Yue-Feng Zhu,
  • Si-Yuan Hu,
  • Huan Zhang,
  • Ya-Xin Cui,
  • Jin Yang,
  • Chen-Yang Shen

摘要

Purpose

Abdominal aortic aneurysm (AAA) is a progressive, age-associated vascular disorder characterized by dilation of the abdominal aorta and a high risk of rupture. RNA-binding motif protein 10 (RBM10), a key regulator of mRNA alternative splicing involved in cell cycle control and apoptosis, has not previously been investigated in AAA. This study aimed to characterize the expression and functional role of RBM10 in AAA pathogenesis.

Methods

RBM10 expression in human AAA tissues was assessed by immunofluorescence. To explore its functional relevance, genome-wide transcriptomic profiling was performed in human aortic smooth muscle cells (HASMCs) transfected with RBM10 adenovirus or negative control for 24 h. The effects of RBM10 on HASMC proliferation and migration were evaluated using MTT and transwell assays, respectively. Apoptosis was quantified by flow cytometry.

Results

RBM10 expression was significantly elevated in human AAA tissues and in an established animal model. RBM10 overexpression markedly suppressed HASMC proliferation and migration while promoting apoptosis. Flow cytometry confirmed enhanced apoptotic rates, consistent with transcriptomic analysis demonstrating activation of the p53 pathway. Upregulation and activation of p53 were validated at the protein level.

Conclusions

These findings indicate that RBM10 contributes to AAA progression by promoting smooth muscle cell apoptosis, likely through a p53-dependent mechanism. RBM10 may represent a promising therapeutic target for preventing or slowing AAA development.