ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm

Citrate levels were abnormally increased in both human and mouse aortic aneurysm tissues.

• Downregulation of ANK, a citrate transporter, was observed in vascular smooth muscle cells (VSMCs) of aneurysmal tissues.
• Knockout of ANK in VSMCs promoted the formation of aortic aneurysms in both Ang II- and CaPO-induced models.
• Overexpression of ANK inhibited the development of aneurysms.
• Deficiency of ANK in VSMCs led to the accumulation of citrate in the cytosol, which was converted into acetyl coenzyme A.
• Increased acetyl coenzyme A intensified histone acetylation and activated inflammatory gene transcription in VSMCs.
• Suppressing citrate cleavage reduced inflammatory gene expression and limited aortic aneurysm formation associated with ANK deficiency.

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