Abstract: SA-PO332
Impact of Oxidative Stress on Vascular Calcification in the Setting of Coexisting CKD and Diabetes Mellitus
Session Information
- Hypertension and CVD: Mechanisms
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Watanabe, Shuhei, Kobe University Graduate School of Medicine, Kobe, Japan
- Fujii, Hideki, Kobe University Graduate School of Medicine, Kobe, Japan
- Kono, Keiji, Kobe University Graduate School of Medicine, Kobe, Japan
- Watanabe, Kentaro, Kobe University Graduate School of Medicine, Kobe, Japan
- Goto, Shunsuke, Kobe University Graduate School of Medicine, Kobe, Japan
- Nishi, Shinichi, Kobe University Graduate School of Medicine, Kobe, Japan
Background
Vascular calcification is a crucial complication in patients with chronic kidney disease (CKD). Particularly, CKD patients with diabetes mellitus (DM) manifest severe vascular calcification but its precise mechanisms are poorly understood. It has been reported that oxidative stress plays a key role for the progression of vascular calcification. In the present study, we investigated the pathophysiological mechanisms of vascular calcification in the setting of coexisting CKD and DM particularly from the perspective of oxidative stress.
Methods
Sprague-Dawley rats were randomly divided into six groups as follows; (i) control rats (control group), (ii) 5/6 nephrectomized rats (CKD group), (iii) streptozotocin (STZ) injected rats (DM group), (iv) 5/6 nephrectomized and STZ injected rats (DM+CKD group), (v) DM+CKD rats treated with insulin (DM+CKD+INS group), (vi) DM+CKD rats treated with apocynin, which is an inhibitor of NADPH oxidase (DM+CKD+APO group). All groups were fed a high phosphate diet from 11 weeks of age. At 18 weeks, the rats were sacrificed for blood and urine analysis, histopathological analysis and evaluating mRNA expressions of oxidative stress and osteoblast differentiation-related markers in the aorta.
Results
Von Kossa-positive mineralized area and calcium content of aorta were significantly increased in the DM+CKD group compared to the control, CKD and DM groups at 18 weeks. However, despite high serum glucose levels control, apocynin treatment prevented the progression of vascular calcification. The mRNA expressions of RUNX2 and ALP and the number of RUNX2-positive cells in the aorta were significantly increased in the DM+CKD group compared to the control, CKD and DM groups. Similarly, these expressions were significantly reduced by apocynin treatment. As for the assessment of oxidative stress, urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), the number of 8-OHdG positive cells in the aorta, and the mRNA expressions of NOX4 and NADPH p22 phox were significantly decreased in the DM+CKD+APO group compared to the DM+CKD group.
Conclusion
Our results suggest that coexisting CKD and DM accelerates vascular calcification mainly by increased oxidative stress.