Abdominal aortic aneurysms (AAAs) occur in 1-2% of the elderly. The rupture of an AAA usually causes uncontrollable lethal hemorrhage, and its risk increases with AAA size. However, there is no effective pharmacological therapy for hindering AAA growth. Here we show that global or vascular smooth muscle cell (VSMC)-specific transient receptor potential melastatin 7 (TRPM7) knockout in mice prevented AAA formation, as indicated by inhibited VSMC reprogramming, reduced inflammatory infiltration and suppressed matrix degradation. Mechanistically, we showed that TRPM7-mediated Ca