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Updated: Sep 16, 2025
Porcine Model of Infrarenal Abdominal Aortic Aneurysm
Published on: November 21, 2019
miR-3154: Novel Pathogenic and Therapeutic Target in Abdominal Aortic Aneurysm
QingBin Hou1,2, Yisi Liu1, Jingjin Hou1
1State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China (Q.H., Y.L., J.H., H.S., Y.Z., J.L., X.Z., C.Y., Y.H.).
Background:
Abdominal aortic aneurysm (AAA) is a life-threatening condition with no effective pharmacological treatments currently available, likely due to our incomplete understanding of the molecular mechanisms underlying AAA pathogenesis and progression. In many cardiovascular diseases, circulatory microRNAs are potential diagnostic and prognostic biomarkers. Therefore, we investigated novel microRNAs with diagnostic and therapeutic potential in AAA.
Methods:
We performed microRNA expression analysis in aorta specimens isolated from mice with saline-induced or Ang II (angiotensin II)-induced AAA, wherein microRNA-3154 (miR-3154) was identified as a potential key molecule in AAA pathogenesis. We used RNA-sequencing analysis, cell migration assays, immunoblotting, protein interactome analysis, coimmunoprecipitation, molecular docking, and molecular dynamics simulation to determine the role of miR-3154 in AAA pathogenesis, clarify the phenotype, and elucidate the underlying molecular mechanisms.
Results:
Using high-throughput sequencing, miR-3154 was identified in the aortic tissue of ApoE-/- mice with AAA as compared with control mice. Increased miR-3154 expression was confirmed in the early-stage Ang II-induced AAA mouse model and the aortic tissues of patients with AAA. Patients with AAA had higher serum miR-3154 level, which positively correlated with computed tomography-estimated size of the aneurysm. Functionally, miR-3154 dose-dependently aggravated vascular smooth muscle cell phenotypic switching and AAA development, both in vivo and in vitro. In vascular smooth muscle cells, TNS1 (tensin-1) was identified as a direct target of miR-3154. Mechanistically, TNS1 interacts with the R1-R13 domain of TLN1 (talin-1), thereby suppressing Sp1 (specificity protein 1) phosphorylation at Thr739 and upregulating MEOX1 (mesenchyme homeobox 1) expression-a key transcription factor regulating vascular smooth muscle cell phenotypic switching.
Conclusions:
We uncovered a novel pathogenic role of miR-3154 in AAA, suggesting its potential as both a therapeutic target and prognostic biomarker.
Insights
MicroRNA-3154 (miR-3154) plays a key role in abdominal aortic aneurysm (AAA) development by promoting vascular smooth muscle cell changes. This finding suggests miR-3154 as a potential diagnostic marker and therapeutic target for AAA.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Biomarker Discovery
Background:
- Abdominal aortic aneurysm (AAA) is a life-threatening condition lacking effective pharmacological treatments.
- Understanding AAA molecular pathogenesis is crucial for developing new therapies.
- Circulating microRNAs are promising biomarkers for cardiovascular diseases.
Purpose of the Study:
- Investigate novel microRNAs for diagnostic and therapeutic potential in AAA.
- Identify key microRNAs involved in AAA pathogenesis.
- Elucidate the molecular mechanisms of microRNA involvement in AAA.
Main Methods:
- MicroRNA expression analysis in mouse models (saline- and Ang II-induced AAA) and human AAA tissues.
- RNA-sequencing, cell migration assays, immunoblotting, and protein interactome analysis.
- Coimmunoprecipitation, molecular docking, and molecular dynamics simulations to determine molecular mechanisms.
Main Results:
- MicroRNA-3154 (miR-3154) was identified as a key molecule in AAA pathogenesis.
- Increased miR-3154 expression in AAA mouse models and human AAA tissues; serum miR-3154 correlated with aneurysm size.
- miR-3154 aggravated vascular smooth muscle cell phenotypic switching and AAA development, targeting TNS1.
Conclusions:
- A novel pathogenic role for miR-3154 in AAA was uncovered.
- miR-3154 shows potential as a therapeutic target for AAA.
- miR-3154 may serve as a prognostic biomarker for AAA.
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