ANPEP and coronary artery disorder: Circulating APN levels were negatively correlated with plasma MMP-2 and MMP-9 activities in patients with obesity50 and coronary artery disease (CAD)51, and APN inhibited angiotensin-II-induced cardiac fibrosis through the suppression of MMP-2/9 activities in mice52 Therefore, the absence of APN-dependent anti-inflammatory and anti-MMPs effects might accelerate retinal claudin-5 degradation and the significant increase in vascular permeability, both of which were observed in STZ-induced diabetic APN-KO mice.