Ras-related protein 2 limits vascular smooth muscle cell phenotypic switching and abdominal aortic aneurysm development

Abdominal aortic aneurysm (AAA) and the attendant catastrophic event of rupture remain a leading cause of death. Germline mutation of RRAS2 cause Noonan Syndrome, yet little is known about its function in AAA pathogenesis. Integrated analysis of RNA-seq data revealed RRAS2 a potential regulator of AAA. Its mRNA and protein levels reduced in abdominal aorta of AAA patients and AAA mice. Mice with SMCs-specific knockout of Rras2 were more vulnerable to Ang II and porcine pancreatic elastase-induced AAA, while overexpression of Rras2 in SMCs inhibited AAA progression. Maternally expressed gene 3 (MEG3) prevented RRAS2 mRNA degradation through binding with ELAV-like protein 1 (ELAVL1/HuR). Mechanistically, loss of R-Ras2 reduces phosphorylation, nuclear translocation, and transcriptional activity of general transcription factor 2I (GTF2-I/TFII-I) to reduce contractile-related genes expression in a MET tyrosine kinase-dependent manner. Here, we show an essential role of R-Ras2 in preserving VSMCs homeostasis and provide potential therapeutic targets for AAA.

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Publication Details

Journal
Nature Communications
Published
2025-10-27
DOI
https://doi.org/10.1038/s41467-025-64496-7
Citations
1
Primary Topic
Aortic aneurysm repair treatments
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article
Field-Weighted Citation Impact
1.52
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article

Ras-related protein 2 limits vascular smooth muscle cell phenotypic switching and abdominal aortic aneurysm development

Dongjin Wang, Yi Han, Aihua Gu, Yong Ji et al.
1 citations
Nature Communications
Aortic aneurysm repair treatments
1.52
article

Ras-related protein 2 limits vascular smooth muscle cell phenotypic switching and abdominal aortic aneurysm development

Dongjin Wang, Yi Han, Aihua Gu, Yong Ji, Ke Zhong, Xiaoqi Wu, Tianyu Song, Liping Xie, Feng Chen, Li Li, Rui Li, Yan Zhang, Jinwei Tian, Shanshan Luo, Zhi‐Ren Zhang, Jiyu Chen, Xue Feng, Xinlong Tang, Zhongxu Sun, Shan-zhen Sun
article en
1 citations

Abstract

Abdominal aortic aneurysm (AAA) and the attendant catastrophic event of rupture remain a leading cause of death. Germline mutation of RRAS2 cause Noonan Syndrome, yet little is known about its function in AAA pathogenesis. Integrated analysis of RNA-seq data revealed RRAS2 a potential regulator of AAA. Its mRNA and protein levels reduced in abdominal aorta of AAA patients and AAA mice. Mice with SMCs-specific knockout of Rras2 were more vulnerable to Ang II and porcine pancreatic elastase-induced AAA, while overexpression of Rras2 in SMCs inhibited AAA progression. Maternally expressed gene 3 (MEG3) prevented RRAS2 mRNA degradation through binding with ELAV-like protein 1 (ELAVL1/HuR). Mechanistically, loss of R-Ras2 reduces phosphorylation, nuclear translocation, and transcriptional activity of general transcription factor 2I (GTF2-I/TFII-I) to reduce contractile-related genes expression in a MET tyrosine kinase-dependent manner. Here, we show an essential role of R-Ras2 in preserving VSMCs homeostasis and provide potential therapeutic targets for AAA.

Nature CommunicationsVol. 16(1)
Nanjing University of Chinese Medicine (CN), Southwest University (CN), Harbin Medical University (CN), Renji Hospital (CN), Nanjing Drum Tower Hospital (CN), Second Affiliated Hospital of Harbin Medical University (CN), Heilongjiang University (CN), Nanjing Medical University (CN)
Openalex Percentile: Top 13%
Aortic aneurysm repair treatments
1.52
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