MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion
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Updated: May 24, 2026
Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
Published on: May 16, 2025
Lars Maegdefessel1, Junya Azuma, Ryuji Toh
1Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
Identification and treatment of abdominal aortic aneurysm (AAA) remains among the most prominent challenges in vascular medicine. MicroRNAs are crucial regulators of cardiovascular pathology and represent possible targets for the inhibition of AAA expansion. We identified microRNA-21 (miR-21) as a key modulator of proliferation and apoptosis of vascular wall smooth muscle cells during development of AAA in two established murine models. In both models (AAA induced by porcine pancreatic elastase or infusion of angiotensin II), miR-21 expression increased as AAA developed. Lentiviral overexpression of miR-21 induced cell proliferation and decreased apoptosis in the aortic wall, with protective effects on aneurysm expansion. miR-21 overexpression substantially decreased expression of the phosphatase and tensin homolog (PTEN) protein, leading to increased phosphorylation and activation of AKT, a component of a pro-proliferative and antiapoptotic pathway. Systemic injection of a locked nucleic acid-modified antagomir targeting miR-21 diminished the pro-proliferative impact of down-regulated PTEN, leading to a marked increase in the size of AAA. Similar results were seen in mice with AAA augmented by nicotine and in human aortic tissue samples from patients undergoing surgical repair of AAA (with more pronounced effects observed in smokers). Modulation of miR-21 expression shows potential as a new therapeutic option to limit AAA expansion and vascular disease progression.
Insights
MicroRNA-21 (miR-21) plays a key role in abdominal aortic aneurysm (AAA) development by regulating vascular cell proliferation and apoptosis. Modulating miR-21 offers a potential therapeutic strategy for AAA treatment.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Vascular Biology
Background:
- Abdominal aortic aneurysm (AAA) presents significant challenges in vascular medicine.
- MicroRNAs are critical regulators of cardiovascular diseases, offering potential therapeutic targets.
- MicroRNA-21 (miR-21) is implicated in vascular smooth muscle cell proliferation and apoptosis.
Purpose of the Study:
- To investigate the role of miR-21 in the development of abdominal aortic aneurysm (AAA).
- To explore the therapeutic potential of modulating miR-21 for AAA treatment.
Main Methods:
- Utilized two murine models of AAA (porcine pancreatic elastase and angiotensin II infusion).
- Assessed miR-21 expression levels during AAA development.
- Manipulated miR-21 levels using lentiviral vectors and antagomirs.
- Examined the effects on vascular smooth muscle cell proliferation, apoptosis, and PTEN/AKT pathway.
- Analyzed human aortic tissue samples from AAA patients.
Main Results:
- miR-21 expression increased with AAA development in murine models.
- Overexpression of miR-21 promoted vascular cell proliferation, reduced apoptosis, and protected against aneurysm expansion.
- miR-21 regulated the PTEN/AKT pathway, influencing cell survival and proliferation.
- Inhibition of miR-21 exacerbated AAA progression.
- Similar miR-21 effects were observed in human AAA tissues, particularly in smokers.
Conclusions:
- miR-21 is a key regulator of vascular cell behavior in AAA development.
- Targeting miR-21 presents a promising therapeutic avenue for limiting AAA expansion and vascular disease progression.
