Associations Between MicroRNA and Abdominal Aortic Aneurysm Diameter Differ by Sex

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Genetics

Background:

• Abdominal aortic aneurysm (AAA) exhibits significant sex-based epidemiological differences, with underlying biological mechanisms largely unknown.
• MicroRNAs (miRNAs) are key regulators of gene expression implicated in AAA pathogenesis, but their sex-specific roles remain under-explored.
• Previous studies on miRNAs and AAA have predominantly focused on male subjects.

Purpose of the Study:

• To investigate sex-specific associations between plasma miRNA levels and aortic diameter in individuals with and without AAA.
• To identify potential biological pathways mediating observed sex differences in miRNA-aortic size relationships.

Main Methods:

• Cross-sectional study involving 242 subjects (85 women, 157 men) with normal aortas or AAA (30-58 mm).
• Clinical data and abdominal aortic diameters (ultrasound) were collected.
• Plasma levels of 17 miRNAs were quantified and analyzed for associations with aortic diameter and sex using multivariable linear regression.

Main Results:

• Associations between six specific miRNAs (miR-125, miR-128-1, miR-24, miR-26a, miR-93, miR-194) and aortic diameter were found to be sex-dependent.
• Bioinformatic analysis suggested the Hippo and TGF-beta signaling pathways are likely influenced by these sex-specific miRNA associations.
• The study identified 35 men and 35 women with AAA, with varying aortic diameters.

Conclusions:

• This study reveals significant sex differences in the relationship between miRNA levels and aortic diameter in the context of AAA.
• The identified sex-specific miRNA associations implicate the Hippo and TGF-beta signaling pathways in AAA development.
• These findings underscore the importance of considering sex as a biological variable in understanding AAA pathogenesis and developing targeted therapies.