Our findings define a critical role of APLN in AAA formation through induction of ACE2 and protection of vascular SMCs, whereas stable APLN analogs provide an effective therapy for vascular diseases.
Previous studies demonstrated that deficiency of angiotensin-converting enzyme 2 (ACE2) augmented angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysm (AAA) formation in hypercholesterolemic mice.
The results showed that ACE2 gene transfer significantly decreased the occurrence of AAAs and inhibited AAA formation in ApoE<sup>-/-</sup> mice by inhibiting the inflammatory response and MMP activation, and the mechanisms may involve decreased ERK and Ang II-nuclear factor kappa B signaling pathways.