MicroRNA-146a Prevents AAA Development Through Repressing VSMC Inflammation.

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Genetics and Genomics

Background:

• Vascular smooth muscle cell (VSMC) homeostasis is crucial for preventing abdominal aortic aneurysms (AAA).
• MicroRNA 146a (miR-146a) levels are altered in AAA patients, but its specific role in VSMC homeostasis and AAA development is unclear.

Purpose of the Study:

• To investigate the role of miR-146a in maintaining VSMC homeostasis.
• To determine the impact of miR-146a on the development and progression of abdominal aortic aneurysms (AAA).

Main Methods:

• Assessed miR-146a expression in plasma and aortas of mouse models of AAA.
• Utilized ApoE-/- MiR-146a-/- double knockout mice to evaluate AAA progression.
• Employed transcriptomics analysis to elucidate miR-146a's mechanisms in VSMC homeostasis.
• Conducted in vitro experiments using miR-146a mimics and TNFα stimulation.

Main Results:

• MiR-146a expression was elevated in VSMCs within aneurysm tissues from patients and mouse models.
• Knockout of miR-146a exacerbated AAA incidence and severity in ApoE-/- mice.
• miR-146a mimic inhibited TNFα-induced VSMC inflammation, apoptosis, and dedifferentiation.
• miR-146a suppressed the NF-κB/NLRP3 signaling pathway by reducing IRAK-1 and TRAF-6.
• Local administration of miR-146a agomir inhibited AAA dilatation in vivo.

Conclusions:

• MiR-146a plays a protective role against AAA formation and progression by preserving VSMC homeostasis.
• Upregulating miR-146a in the aorta presents a potential therapeutic avenue for limiting AAA expansion.