Influence of oxidative stress on vascular calcification in the setting of coexisting chronic kidney disease and diabetes mellitus
Shuhei Watanabe, Hideki Fujii, Keiji Kono, Kentaro Watanabe, Shunsuke Goto, Shinichi Nishi
Abstract
Vascular calcification (VC) is a common complication in patients with chronic kidney disease (CKD). Particularly, CKD patients with diabetes mellitus (DM) develop severe VC. Specific mechanisms of VC remain unclear; this study aimed to investigate them in the context of coexisting CKD and DM, mainly regarding oxidative stress. Sprague Dawley rats were randomly divided into six groups as follows: control rats (Control), 5/6 nephrectomized rats (CKD), streptozotocin-injected rats (DM), 5/6 nephrectomized and streptozotocin-injected rats (CKD + DM), CKD + DM rats treated with insulin (CKD + DM + INS), and CKD + DM rats treated with antioxidant apocynin (CKD + DM + APO). At 18 weeks old, the rats were sacrificed for analysis. Compared to the control, DM and CKD groups, calcification of aortas significantly increased in the CKD + DM group. Oxidative stress and osteoblast differentiation-related markers considerably increased in the CKD + DM group compared with the other groups. Moreover, apocynin considerably reduced oxidative stress, osteoblast differentiation-related markers, and aortic calcification despite high blood glucose levels. Our data indicate that coexisting CKD and DM hasten VC primarily through an increase in oxidative stress; anti-oxidative therapy may prevent the VC progression.