AIM2 regulates vascular smooth muscle cell migration in atherosclerosis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Biology

Background:

• Atherosclerosis (AS) is a primary cause of cardiovascular and cerebrovascular diseases.
• Vascular smooth muscle cell (VSMC) migration drives atherosclerotic plaque formation and progression.
• Absent in melanoma 2 (AIM2) is known for inflammasome activation, but its role beyond this in AS is unexplored.

Purpose of the Study:

• To investigate the role and mechanism of AIM2 in atherosclerotic plaque progression.
• To explore AIM2's function in vascular smooth muscle cells (VSMCs) independent of inflammasome activity.

Main Methods:

• Utilized apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet, with lentiviral vectors for AIM2 overexpression or knockdown.
• Conducted in vitro studies on VSMCs, including exposure to oxidized low-density lipoprotein (ox-LDL) and assessment of cell migration.
• Analyzed atherosclerotic lesion size, VSMC count, MMP2 expression, and the TGF-β/SMAD signaling pathway.

Main Results:

• AIM2 overexpression increased aortic atherosclerotic lesion area and VSMC count in ApoE-/- mice.
• AIM2 promoted VSMC migration in vitro, an effect influenced by oxidative stress (ROS) and high glucose.
• AIM2 modulated the TGF-β/SMAD signaling pathway in VSMCs.

Conclusions:

• AIM2 significantly contributes to atherosclerotic plaque progression.
• AIM2 promotes AS by enhancing VSMC migration.
• AIM2 represents a potential therapeutic target for atherosclerosis.