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Published on: June 29, 2014
Osborne-Mendel rats simultaneously develop cardiac and renal dysfunction, left atrial thrombosis, peripheral artery
Makoto Asahina1, Hideki Matsumoto1, Yoshitaka Yasuhara1
1Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
Abstract:
Although chronic kidney disease (CKD) is strongly associated with onsets of cardiovascular disease (CVD), the pathogenic mechanism between these diseases has not been fully understood. To develop and validate new therapeutic strategies for this complication, appropriate experimental models that reflect the complexity of the underlying pathophysiology are needed. The Osborne-Mendel (OM) rat was identified as an atherosclerosis-prone and a premature-death rat strain among 16 inbred rat strains when fed high-cholesterol containing diet. When fed high-cholesterol diet, OM rats showed simultaneous occurrence of aortic aneurysm, aortic dissection, peripheral artery occlusion, and left atrial thrombosis. OM rats had significantly lower max dP/dt and higher min dP/dt than F344 rats did, indicating impaired left ventricle contractility and relaxation. OM rats developed renal dysfunction, showing increased urinary albumin excretion. OM rats also showed mild hypertension, decreased endothelial function, and enhanced coagulation and platelet aggregation, compared with F344 rats. We now report that OM rat would be a novel spontaneous animal model which simultaneously demonstrates cardiac and renal dysfunction, and CVD events. This model could be a useful model for the pre-clinical testing of pharmacological therapies and could provide new insight into potential targets and pathways for the treatment of CKD and CVD.
Insights
The Osborne-Mendel rat, fed a high-cholesterol diet, spontaneously develops cardiovascular disease (CVD) and renal dysfunction. This atherosclerosis-prone rat strain offers a novel model for studying chronic kidney disease (CKD) and CVD comorbidities.
Area of Science:
- Nephrology
- Cardiology
- Animal Models
Background:
- Chronic kidney disease (CKD) and cardiovascular disease (CVD) are closely linked, but the underlying mechanisms remain unclear.
- Developing effective therapeutic strategies requires experimental models that accurately mimic the complex pathophysiology of these co-occurring conditions.
Purpose of the Study:
- To identify and validate a novel animal model that spontaneously exhibits both cardiac and renal dysfunction, along with cardiovascular events.
- To establish a suitable model for pre-clinical testing of pharmacological therapies targeting CKD and CVD.
Main Methods:
- Evaluation of 16 inbred rat strains fed a high-cholesterol diet.
- Assessment of cardiovascular parameters including aortic aneurysm, dissection, peripheral artery occlusion, left atrial thrombosis, cardiac contractility (dP/dt), hypertension, and endothelial function.
- Analysis of renal function markers such as urinary albumin excretion.
- Comparison of Osborne-Mendel (OM) rats with F344 rats.
Main Results:
- Osborne-Mendel (OM) rats were identified as atherosclerosis-prone and exhibited premature death on a high-cholesterol diet.
- OM rats simultaneously developed aortic aneurysm, dissection, peripheral artery occlusion, and left atrial thrombosis.
- OM rats displayed impaired cardiac contractility, renal dysfunction (increased albuminuria), mild hypertension, decreased endothelial function, and enhanced coagulation/platelet aggregation compared to F344 rats.
Conclusions:
- The OM rat is a novel spontaneous animal model that concurrently demonstrates cardiac and renal dysfunction, and cardiovascular disease events.
- This model serves as a valuable tool for pre-clinical evaluation of pharmacological treatments for CKD and CVD.
- The OM rat model may offer new insights into therapeutic targets and pathways for managing comorbid CKD and CVD.
