miR-133a Replacement Attenuates Thoracic Aortic Aneurysm in Mice

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Extracellular Matrix Remodeling

Background:

• Thoracic aortic aneurysms (TAAs) involve abnormal extracellular matrix remodeling and myofibroblast activation.
• MicroRNA miR-133a, crucial for cellular phenotype regulation, is decreased in clinical TAA samples.

Purpose of the Study:

• To investigate if miR-133a modulates aortic fibroblast phenotype.
• To determine if lentiviral overexpression of miR-133a can attenuate TAA development in a murine model.

Main Methods:

• Induction of TAA in mice and analysis of miR-133a levels and fibroblast markers.
• Isolation and phenotypic characterization of aortic fibroblasts with miR-133a manipulation.
• In vivo assessment of miR-133a overexpression via lentivirus in a TAA mouse model.
• Luciferase reporter assay to identify miR-133a targets, specifically furin.

Main Results:

• miR-133a levels were inversely correlated with aortic diameter in TAA.
• Reduced miR-133a in TAA fibroblasts increased migration and collagen contraction.
• Overexpression of miR-133a attenuated TAA progression in vivo.
• Furin was identified as a miR-133a target, and its repression by miR-133a reduced proteolytic activation.

Conclusions:

• miR-133a plays a key role in regulating aortic fibroblast phenotype.
• miR-133a restoration effectively prevented TAA development in a murine model.
• Targeting miR-133a offers a potential novel therapeutic strategy for thoracic aortic aneurysms.