Abstract: SA-PO336
A Novel and Reproducible Model of CKD-Induced Vascular Calcification in Mice
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
- Abou Daya, Farah, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Spangler, Daryll R., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Black, Laurence Marie, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Traylor, Amie, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Zarjou, Abolfazl, University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Vascular calcification remains a frequent complication of advanced chronic kidney disease (CKD) and a leading cause of morbidity and mortality in this population. Various animal models have been introduced to induce CKD and study the pathomechanism of vascular calcification. The most commonly used such model in rodents is 5/6 nephrectomy followed by using high phosphate diet. However, the 5/6 nephrectomy in mice is markedly challenging and results are seldom consistent.
Methods
To address this challenge, we sought to examine a novel model of vascular calcification where ten-week-old mice with DBA2 background that are prone to vascular calcification, underwent unilateral ischemia reperfusion injury (UIRI) for 25 minutes followed by complete right nephrectomy after one week. The control group underwent sham surgery and both groups were fed high phosphate diet (0.6% Ca, 0.9% Pi) for twelve weeks at which point mice were sacrificed for analysis.
Results
While serum creatinine did not reveal significant changes (treatment group = 0.12 ± 0.01 mg/dL vs control group = 0.13 ± 0.03 mg/dL), glomerular filtration rate measurements (GFR) were lower in the treatment groups (treatment group = 187.68 ± 31.99 uL/min vs control group = 230.99 ±18.5 uL/min). Furthermore, protein analysis on aortae of the mice demonstrated significant upregulation of osteogenic markers including osteocalcin, alkaline phosphatase, and osteoblast specific transcription factor, cbfa-1.
Conclusion
Our findings suggest that UIRI followed by nephrectomy is a feasible and reproducible model of vascular calcification associated with CKD that would enable study of various transgenic mice to better understand the mechanistic pathways involved in mineralization of vascular tree and targeting novel therapeutics.
Funding
- Other NIH Support