The Cardiometabolic Disease Models Core in NHRIS will provide guidance, training and service in cardiometabolic cell and animal disease models needed to support pre-clinical and translational research in the area of Cardiometabolic Diseases including acute myocardial infarction, left ventricular hypertrophy, heart failure with preserved ejection fraction (HFpEF), diabetic cardiomyopathy and peripheral arterial disease.
Prof Derek Hausenloy Dr Elisa Liehn Dr Chrishan Ramachandra Dr Sauri Hernandez-Resendiz
Small animal Cardiometabolic Disease models platform (led by Dr Elisa Liehn and Dr Sauri Hernandez-Resendiz)
This platform will support research themes requiring small animal (mice and rats) models for acute myocardial infarction (AMI),
ex vivo and simulated ischemia-reperfusion injury, post-infarct left ventricular (LV) remodelling, left ventricular hypertrophy (LVH), diabetic cardiomyopathy (DMC), diabetic peripheral arterial disease (DM PAD), Atherosclerosis, heart failure with preserved ejection fraction (HFpEF). This platform will provide shared facilities for small animal echocardiography, ECG monitoring, pressure-volume (PV) loop analysis, animal histology, animal imaging, microscopy, isolation of cardiomyocytes/endothelial cells/cardiac fibroblasts, and assessment of myofibril mechanics. Services include experimental design and protocol assistance.
Human induced pluripotent stem cell (iPSC) platform (led by Dr Chrishan Ramachandra)
This platform will allow disease modelling of various cardiac diseases including hypertrophic cardiomyopathy (HCM), DMC, and HFpEF. It will provide phenotypic characterisation of iPSC-derived cardiomyocytes and endothelial cells, new insights into underlying pathophysiology, discovery of novel therapeutic targets and treatments, and a platform for screening tool compounds.
Small animal Cardiometabolic Disease models platform
- AMI induced by coronary ligation, and post-infarct adverse LV remodelling in mice and rats
Ex vivo heart perfusion by Langendorff system
- Simulated ischemia-reperfusion injury
in vitro assay
- Pressure-overload LVH induced by transverse aortic constriction (TAC) in mice and rats
- PAD induced by femoral artery ligation with peripheral blood flow measured by Periscan in mice and rats.
- Carotid and aortic atherosclerosis induced by carotid-wire injury and high-fat diet in mice and rats.
- Carotid and aortic stenting in models of atherosclerosis in mice and rats.
- Small animal models of HFpEF (high-fat diet and L-NAME)
- Assess cardiac function using echocardiography and PV Loops in mice and rats.
- Assessment of myofibril mechanics using myofibril rig.
- Isolation of cardiomyocytes, cardiac fibroblasts and endothelial cells.
- Histological and microscopic assessment of heart and vascular atheroma tissue and cells.
Human induced pluripotent stem cell (iPSC) platform
- Generation of human iPSCs and differentiation into cardiomyocytes or endothelial cells.
- Phenotypic characterisation:
(i) Structural features (e.g. hypertrophy, sarcomere organisation, multinucleation);
(ii) Calcium handling and cellular contractility;
(iii) Myofibril mechanics;
(iv) Endothelial function;
(v) Metabolism and bioenergetics.
- Screening platform for tool compounds targeting cardiometabolic disease.
- Screening platform to determine phenotypic significance of new genetic variants (e.g HCM and DCM).
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