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Updated: Jul 19, 2025
The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Cardiovascular changes in the NZB/W F1 mouse model of lupus nephritis
Romy Böhme1, Christoph Daniel1, Fulvia Ferrazzi1,2
1Department of Nephropathology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Insights
Systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) show cardiovascular changes linked to kidney damage. Cardiac inflammation and complement deposition also contribute to cardiovascular disease in SLE.
Area of Science:
- Immunology
- Nephrology
- Cardiology
Background:
- Systemic lupus erythematosus (SLE) increases cardiovascular (CV) disease risk.
- Lupus nephritis (LN) is a common complication of SLE and an additional CV risk factor.
- The distinct roles of LN and SLE in CV events remain unclear.
Purpose of the Study:
- To investigate the impact of lupus nephritis (LN) on cardiovascular changes in a mouse model.
- To differentiate the contributions of renal impairment and lupus-specific factors to CV disease.
Main Methods:
- Utilized female NZBxNZW F1 mice (lupus model) and NZW mice (controls).
- Performed serologic, morphologic, immunohistologic, and molecular analyses.
- Measured systolic blood pressure and analyzed gene expression and protein deposition.
Main Results:
- NZB/W mice exhibited significant cardiovascular changes (e.g., cardiac hypertrophy, arterial thickening) correlated with renal damage.
- Increased blood pressure and proteinuria occurred with kidney damage progression.
- Upregulation of interferon beta response, IFI202b, IL-6, and complement deposition (CFD, C3c) in the heart correlated with disease severity.
Conclusions:
- Renal impairment (LN) significantly contributes to cardiovascular disease pathogenesis in SLE.
- Lupus-specific cardiac inflammation and complement deposition are also key factors in CV disease development.
Background:
Patients with systemic lupus erythematosus (SLE), an autoimmune disease, have a higher risk of cardiovascular (CV) disease and death. In addition, up to 40%-50% of SLE patients develop lupus nephritis (LN) and chronic kidney disease, which is an additional CV risk factor. Thus, the individual contributions of LN and other SLE-specific factors to CV events are unclear.
Methods:
In this study, we investigated the effect of LN on the development of CV changes using the female NZBxNZW F1 (NZB/W) mouse model of lupus-like disease, with female NZW mice as controls. Standard serologic, morphologic, immunohistologic, and molecular analyses were performed. In a separate group of NZB/W mice, systolic blood pressure (BP) was measured during the course of the disease using tail plethysmography.
Results:
Our data show marked CV changes in NZB/W mice, i.e., increased heart weight, hypertrophy of the left ventricle (LV) and septum, and increased wall thickness of the intramyocardial arteries and the aorta, which correlated with the progression of renal damage, but not with the age of the mice. In addition, systolic BP was increased in NZB/W mice only when kidney damage progressed and proteinuria was present. Pathway analysis based on gene expression data revealed a significant upregulation of the response to interferon beta in NZB/W mice with moderate kidney injury compared with NZB mice. Furthermore, IFI202b and IL-6 mRNA expression is correlated with CV changes. Multiple linear regression analysis demonstrated serum urea as a surrogate marker of kidney function and IFI202b expression as an independent predictor for LV wall thickness. In addition, deposition of complement factors CFD and C3c in hearts from NZB/W mice was seen, which correlated with the severity of kidney disease.
Conclusions:
Thus, we postulate that the pathogenesis of CV disease in SLE is affected by renal impairment, i.e., LN, but it can also be partly influenced by lupus-specific cardiac expression of pro-inflammatory factors and complement deposition.
