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MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion
Lars Maegdefessel1, Junya Azuma, Ryuji Toh
1Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science Translational Medicine
|February 24, 2012
Summary
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.
