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Updated: Jun 7, 2026
A Mouse Abdominal Aortic Aneurysm Model by Periadventitial Calcium Chloride and Elastase Infiltration
Published on: August 2, 2024
Identification and characteristics of microRNAs with altered expression patterns in a rat model of abdominal aortic
Guang Liu1, Ying Huang, Xinwu Lu
1Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, PR China.
Abstract:
Abdominal aortic aneurysm (AAA) is a lethal disease, occurring mostly in men more than 65 years of age. Until recently, the pathogenesis of AAA remains poorly understood. MicroRNAs (miRNAs) are a novel class of endogenous small non-coding RNAs that play important roles in diverse biological and pathological processes including cardiovascular diseases. However, their biological roles in AAA formation have not been elucidated. In this study, we employed oligonucleotide microarrays to detect and compare miRNA expression profiles in a rat model of AAA. The abdominal aorta was exposed and incubated for 20 min with saline supplemented with calcium chloride and collagenase. After 28 days, the treated aortas were evaluated by digital measurement and angiography. A 50% increase over the normal diameter is considered as AAA. Our results revealed a set of differentially expressed miRNAs, with 10 significantly up-regulated and 5 significantly down-regulated miRNAs in AAA tissues. Four miRNAs (miR-19a, miR-19b, miR-132, and miR-221) were randomly selected for validation using real-time RT-PCR. Functional annotations of all putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that predicted targets were highly enriched and involved in several key signaling pathways important for AAA formation, including pathways in cancer and signaling pathways involving mitogen-activated protein kinase, Wnt, neurotrophin, and ErbB. In summary, this study indicates that miRNAs might contribute to AAA formation probably by affecting multiple target genes and signaling pathways, which is expected to provide new clues to develop targeted therapies against this calamitous disease.
Insights
MicroRNAs (miRNAs) play a role in abdominal aortic aneurysm (AAA) formation. This study identified differentially expressed miRNAs in a rat AAA model, suggesting potential therapeutic targets for this lethal cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Disease Pathogenesis
Background:
- Abdominal aortic aneurysm (AAA) is a significant cause of mortality, primarily affecting older men.
- The underlying mechanisms of AAA development have been poorly understood until recently.
- MicroRNAs (miRNAs) are recognized regulators of biological processes, including cardiovascular disease, but their specific role in AAA remains unclear.
Purpose of the Study:
- To investigate the expression profiles of microRNAs (miRNAs) in a rat model of abdominal aortic aneurysm (AAA).
- To identify specific miRNAs that are differentially expressed during AAA formation.
- To explore the potential functional roles of these miRNAs and their targets in AAA pathogenesis.
Main Methods:
- Oligonucleotide microarrays were used to compare miRNA expression in AAA tissues versus normal aortic tissues in a rat model.
- AAA was induced using calcium chloride and collagenase incubation of the abdominal aorta.
- Digital measurement and angiography were employed for AAA evaluation, with a 50% diameter increase defining AAA.
- Real-time RT-PCR was used to validate the expression of selected miRNAs.
- Bioinformatics approaches were utilized for functional annotation of predicted miRNA targets.
Main Results:
- A distinct set of differentially expressed miRNAs was identified in AAA tissues compared to controls.
- Ten miRNAs were significantly upregulated, and five were significantly downregulated in AAA tissues.
- Four specific miRNAs (miR-19a, miR-19b, miR-132, and miR-221) were validated.
- Functional analysis revealed that predicted targets of these miRNAs are involved in key signaling pathways implicated in AAA, such as pathways in cancer, MAPK, Wnt, neurotrophin, and ErbB signaling.
Conclusions:
- MicroRNAs (miRNAs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA).
- Differential expression of miRNAs suggests their contribution to AAA formation through the regulation of multiple target genes and signaling pathways.
- These findings offer novel insights for the development of targeted therapeutic strategies against AAA.
