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Updated: Sep 2, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Uremic mouse model to study vascular calcification and "inflamm-aging"
Markus Tölle1, Cornelia Henkel1, Jaqueline Herrmann1
1Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Cooperate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
Insights
This study introduces a new adenine-induced mouse model for chronic uremia, revealing significant vascular calcification and inflammation. This model aids in understanding disease progression and testing therapies for cardiovascular complications.
Area of Science:
- Cardiovascular Biology
- Nephrology
- Animal Models
Background:
- Vascular calcification and chronic inflammation are key risk factors for cardiovascular mortality, particularly in chronic uremia patients.
- Current treatment options for preventing rapid disease progression are limited.
Purpose of the Study:
- To evaluate an adenine-based mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) in aortic tissue.
- To unravel molecular pathogenesis and provide a model for therapy testing in chronic uremia.
Main Methods:
- Dietary adenine administration to DBA2/N mice to induce chronic uremia.
- Analysis of uremia blood markers, renal fibrosis, crystal deposits, medial vessel calcification, and elastin organization.
- Assessment of osteogenic markers (Bmp-2, Sox-9), senescence marker (p21), and pro-inflammatory proteins (serum amyloid A, Il-1β, Il-6).
Main Results:
- Adenine feeding induced stable chronic uremia with elevated blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone.
- Uremia led to renal fibrosis, crystal deposits, moderate-to-severe medial vessel calcification, and elastin disorganization.
- Increased expression of osteogenic markers (Bmp-2, Sox-9), senescence marker (p21), and pro-inflammatory proteins (serum amyloid A, Il-1β, Il-6) was observed.
Conclusions:
- The adenine-induced mouse model effectively replicates chronic uremia, vascular calcification, and inflammation.
- This model offers a valuable platform for investigating signaling pathways in vascular disease and for preclinical therapeutic intervention studies.
Abstract:
Calcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to severe medial vessel calcification and subsequent elastin disorganization. In addition, expression of osteogenic markers as Bmp-2 and its transcription factor Sox-9 as well as p21 as senescence marker were increased in uremic mice compared to controls. Pro-inflammatory uremic proteins such as serum amyloid A, interleukin (Il)-1β, and Il-6 increased. This novel model of chronic uremia provides a simple method for investigation of signaling pathways in vascular inflammation and calcification and therefore offers an experimental basis for the development of potential therapeutic intervention studies.
