Student research project
Supervisor(s): Morag Young and Monica Kanki
Project summary
A new model of HFpEF-like heart disease combines low NO (N[w]-nitro-l-arginine methyl ester, L-NAME) with 16wk high fat feeding (HFF) to identify mechanisms that promote the phenotype of HFpEF in adult (16wk–~32wk) male and female mice (1). By combining obesity, metabolic dysfunction and reduced nitric oxide signalling, this model recapitulates the metabolic and cellular mechanisms leading to HFpEF. However, this model has not been validated in house nor has it been investigated in aged (9–12-month-old) mice. This is important given that there are significant differences in cardiac gene expression, inflammation and remodelling pathways between young adult and aged mice. Understanding the mechanisms of HFpEF in an older preclinical model is essential for developing appropriate strategies for HFpEF in the clinic. The in vivo part of this project is complete.
Outcomes will identify the phenotype of the model of “HFpEF” in aged male and female mice. We will gain an understanding of the importance of metabolic and inflammatory changes in the tissues for the phenotype and identify important tissue and sex differences.
Related methods, skills or technologies
This project is suitable for a Masters, Honours or PhD student. This project involves the analysis of heart, kidney and other tissues and serum generated in this study. Laboratory skills include immunostaining and image analysis for inflammatory, tissue injury and other markers of disease, RTPCR and western blot for disease markers that may account for changes in tissue function, analysis of lipidomic profiles and staining and image analysis for structural proteins. Other aspects of this project may include a systematic literature review and analysis of existing datasets..
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