Heart failure is a progressive condition characterised by cardiomyocyte loss and cardiac fibroblast proliferation leading to cardiac hypertrophy and impaired heart function. Cardiac hypertrophy is commonly associated with high blood pressure in response to altered renin-angiotensin system (RAS) activity. However, there is evidence that RAS activity has a role in the early stages of heart failure that is independent of its influence on blood pressure. To investigate this, Justin F. X. Ainscough's group used a conditional mouse model in which a human angiotensin II type-I receptor transgene (HART) was expressed in fully matured cardiomyocytes. Persistent HART activity in young mice causes heart dysfunction without cardiac hypertrophy. This dysfunction correlates with increased expression of pro-angiogenic markers in cardiomyocytes and elicits a compensatory response in non-myocyte cells, which show downregulation of pro-angiogenic genes and inflammatory markers. Noteworthy, this stage is reversible by downregulation of HART expression. Further activation of the receptors, instead, leads to a secondary stage characterised by cardiomyocyte death and activation of fibroblast and inflammatory cells, which leads to further deterioration of heart function. This study therefore identifies an early stage of heart dysfunction associated with increased RAS activity, potentially treatable with RAS inhibitors to prevent heart failure development. Page
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August 2015
Development/DMM Virtual Meeting 2021
Welcoming new Editors to DMM
Editor-in-Chief Liz Patton wants DMM to strengthen its presence in the field of translational biology and to focus on the importance of disease mechanisms, just as much as models. To implement this vision, we are pleased to welcome new Editors Sally Dunwoodie (Victor Chang Cardiac Research Institute, Australia), Monkol Lek (Yale School of Medicine, USA) and Rickie Patani (Francis Crick Institute, London, UK) to the team.
Roles of the gut microbiome in colorectal cancer development
Going hand-in-hand, a new Perspective by Foegeding et al. explores the Western diet as a driver of dysbiosis in colorectal cancer while a new Review by Wang et al. focuses on microbiota-driven mechanisms that initiate sporadic colorectal cancer.
preLights – the latest disease modelling preprints
Head over to preLights for the digests of the latest preprints:
Erin McGregor highlights work by Nowicka et al. that suggests a potential connection between mitochondrial dysfunction and neurodegeneration.
Emma Wilson discusses work by Dagra et al., which highlights D2 receptors as a potential target that could be used to alleviate alpha-Synuclein pathology in Parkinson’s disease.
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