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Updated: Jul 28, 2025
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Cardiovascular characterisation of a novel mouse model that combines hypertension and diabetes co-morbidities
Arpeeta Sharma1,2, Judy S Y Choi3, Anna M D Watson3,4,5
1Group Leader (Oxidative Stress Laboratory), Diabetic Complications Division, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. Arpeeta.sharma@baker.edu.au.
Insights
Researchers developed a new mouse model for studying combined diabetes and hypertension. This model helps investigate cardiovascular damage and test new therapies for these co-existing conditions.
Area of Science:
- Cardiovascular Research
- Diabetology
- Hypertension Research
Background:
- Hypertension is 1.5-2.0 times more prevalent in diabetic patients.
- Co-existing diabetes and hypertension worsen cardiac and vascular injury, leading to heart failure.
- Oxidative stress and inflammation drive pathological cardiac remodeling in these conditions.
Purpose of the Study:
- To develop a novel preclinical mouse model for co-morbid diabetes and hypertension.
- To investigate the cardiac and vascular pathology associated with these co-existing diseases.
- To provide a tool for testing novel therapeutic strategies.
Main Methods:
- Type 1 diabetes induced in spontaneously hypertensive Schlager (BPH/2) mice using streptozotocin.
- Cardiac function assessed by echocardiography after 10 weeks.
- Post-mortem analysis included histology, RT-PCR, and flow cytometry for cardiomyocyte hypertrophy, fibrosis, and inflammation.
Main Results:
- Significantly increased markers of inflammation (MCP-1), oxidative stress (urinary 8-isoprostanes), and fibrosis (CTGF).
- Elevated diastolic dysfunction, indicated by prolonged isovolumic relaxation time (IVRT).
- Demonstrated increased cardiovascular damage in the combined disease model.
Conclusions:
- The developed mouse model effectively mimics co-morbid diabetes and hypertension.
- This model is valuable for testing targeted therapies for cardiovascular complications.
- Facilitates research into novel treatments for debilitating co-morbidities.
Abstract:
Epidemiologic data suggest that the prevalence of hypertension in patients with diabetes mellitus is ∼1.5-2.0 times greater than in matched non-diabetic patients. This co-existent disease burden exacerbates cardiac and vascular injury, leading to structural and functional changes to the myocardium, impaired cardiac function and heart failure. Oxidative stress and persistent low-grade inflammation underlie both conditions, and are identified as major contributors to pathological cardiac remodelling. There is an urgent need for effective therapies that specifically target oxidative stress and inflammation to protect against cardiac remodelling. Animal models are a valuable tool for testing emerging therapeutics, however, there is a notable lack of appropriate animal models of co-morbid diabetes and hypertension. In this study, we describe a novel preclinical mouse model combining diabetes and hypertension to investigate cardiac and vascular pathology of co-morbid disease. Type 1 diabetes was induced in spontaneously hypertensive, 8-week old, male Schlager (BPH/2) mice via 5 consecutive, daily injections of streptozotocin (55 mg/kg in citrate buffer; i.p.). Non-diabetic mice received citrate buffer only. After 10 weeks of diabetes induction, cardiac function was assessed by echocardiography prior to post-mortem evaluation of cardiomyocyte hypertrophy, interstitial fibrosis and inflammation by histology, RT-PCR and flow cytometry. We focussed on the oxidative and inflammatory stress pathways that contribute to cardiovascular remodelling. In particular, we demonstrate that markers of inflammation (monocyte chemoattractant protein; MCP-1), oxidative stress (urinary 8-isoprostanes) and fibrosis (connective tissue growth factor; CTGF) are significantly increased, whilst diastolic dysfunction, as indicated by prolonged isovolumic relaxation time (IVRT), is elevated in this diabetic and hypertensive mouse model. In summary, this pre-clinical mouse model provides researchers with a tool to test therapeutic strategies unique to co-morbid diabetes and hypertension, thereby facilitating the emergence of novel therapeutics to combat the cardiovascular consequences of these debilitating co-morbidities.
