CAPE-pNO2 attenuates diabetic cardiomyopathy through the NOX4/NF-κB pathway in STZ-induced diabetic mice.

Diabetic cardiomyopathy (DCM) is one of the most severe cardiovascular complications in diabetes. Caffeic acid para-nitro phenethyl ester (CAPE-pNO2) could ameliorate diabetic nephropathy in the diabetic mice in our previous study. This paper was aimed to investigate the effect of CAPE-pNO2 on DCM and its potential mechanism. The DCM mice were established by intraperitoneal injection with streptozotocin (STZ, 50 mg/kg) for 5 days. When the fasting blood glucose level remains above 11.1 mmol/L, treated the mice with CAPE and CAPE-pNO2 for 8 weeks, then the mice were executed, and the samples of blood and heart tissue were collected for the subsequent experiments. The results showed that CAPE-pNO2 can alleviate CK, LDH, TC and TG levels, as well as depress the activity of ROS by down-regulating the expression of NOX4 and improving SOD activity in the serum of STZ-induced DCM mice. Meanwhile, it can also reduce the content of MDA and inhibit lipid accumulation. Besides, CAPE-pNO2 could repress the expression of TNF-α, IL-1β and IL-6 IL - 6 via the NOX4/NF-κB pathway to improve the development of inflammation. Furthermore, it can suppress the expression of collagen and fibronectin to inhibit myocardial fibrosis through the TGF-β1/Smad pathway, and inhibit ECM deposition by regulating TGF-β1 directly, as shown in cardiac tissue section. Importantly, the above results showed that CAPE-pNO2 had better effects of reversing pathological changes than CAPE in a significant difference of p < 0.05. In brief, CAPE-pNO2 can prevent the heart injury of DCM mice via the NOX4/NF-κB pathway, and shows the improvement effects of anti-fibrosis, anti-oxidative and anti-inflammatory.