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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Disturbances in Bone Largely Predict Aortic Calcification in an Alternative Rat Model Developed to Study Both
Ellen Neven1, Rida Bashir-Dar1, Geert Dams1
1Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
Insights
A new rat model allows simultaneous study of chronic kidney disease (CKD)-related vascular calcification and bone pathology. This model offers stable CKD, moderate vascular calcification, and measurable bone changes, aiding research into the bone-vascular axis.
Area of Science:
- Nephrology
- Endocrinology
- Biomedical Engineering
Background:
- Current rat models exhibit excessive vascular calcification and chaotic bone mineralization, hindering simultaneous study of the bone-vascular axis in chronic kidney disease (CKD).
- A critical need exists for an animal model that enables concurrent investigation of vascular calcification and bone pathology in CKD.
Purpose of the Study:
- To develop and validate a novel rat model for studying the interrelations between CKD, vascular calcification, and bone disease.
- To establish a model that allows for simultaneous assessment of bone and vascular pathologies in CKD.
Main Methods:
- Chronic kidney disease (CKD) was induced in rats using a 0.25% adenine/low vitamin K diet.
- Vascular calcification was assessed via histomorphometry and arterial calcium content.
- Bone parameters (static and dynamic) were measured at multiple time points (weeks 4, 8, 10, 11, 12).
Main Results:
- The model successfully induced stable, severe CKD with characteristic metabolic derangements (hyperphosphatemia, hypocalcemia, elevated PTH and FGF23).
- Vascular calcification was evident from week 8 onwards, alongside measurable bone pathologies indicative of hyperparathyroid bone disease.
- Bone parameters, specifically eroded perimeter and mineral apposition rate, were identified as significant predictors of aortic calcification.
Conclusions:
- This rat model provides a stable platform for studying CKD complications, exhibiting moderate vascular calcification and quantifiable bone pathology.
- It is the first model suitable for simultaneous mechanistic and intervention studies of vascular calcification and bone disease in CKD.
Abstract:
Because current rat models used to study chronic kidney disease (CKD)-related vascular calcification show consistent but excessive vascular calcification and chaotic, immeasurable, bone mineralization due to excessive bone turnover, they are not suited to study the bone-vascular axis in one and the same animal. Because vascular calcification and bone mineralization are closely related to each other, an animal model in which both pathologies can be studied concomitantly is highly needed. CKD-related vascular calcification in rats was induced by a 0.25% adenine/low vitamin K diet. To follow vascular calcification and bone pathology over time, rats were killed at weeks 4, 8, 10, 11, and 12. Both static and dynamic bone parameters were measured. Vascular calcification was quantified by histomorphometry and measurement of the arterial calcium content. Stable, severe CKD was induced along with hyperphosphatemia, hypocalcemia as well as increased serum PTH and FGF23. Calcification in the aorta and peripheral arteries was present from week 8 of CKD onward. Four and 8 weeks after CKD, static and dynamic bone parameters were measurable in all animals, thereby presenting typical features of hyperparathyroid bone disease. Multiple regression analysis showed that the eroded perimeter and mineral apposition rate in the bone were strong predictors for aortic calcification. This rat model presents a stable CKD, moderate vascular calcification, and quantifiable bone pathology after 8 weeks of CKD and is the first model that lends itself to study these main complications simultaneously in CKD in mechanistic and intervention studies.
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