Project Summary
Establishing the role of the Piezo1 mechanotransducer ion channel in pressure-overload induced left ventricular hypertrophy (LVH) using a mouse model.
What is the issue for NSW?
Pathological left ventricular hypertrophy originates from impaired coupling between heart mechanics and electricity, known as cardiac mechano-electric feedback, and has not been well researched as a potential cause of left ventricular hypertrophy. The heart diseases, including heart failure, associated with left ventricular hypertrophy, present an increasing healthcare burden in western societies, including NSW and other Australian states and territories. This is because cardiovascular disease is the leading cause of death and presents a significant financial and social burden. Pathological left ventricular hypertrophy is the single most important risk factor for cardiovascular mortality. Our project, therefore, presents a great opportunity to use laboratory science achievements for clinical applications towards improving health outcomes and well-being of patients suffering from cardiovascular diseases.
What does the research aim to do and how?
The aim of the proposed research is to determine outstanding causes of pathological ventricular hypertrophy. The focus of our research is the role of Piezo1 and associated TRPM4 channels in activation of downstream signalling processes leading to LVH. To achieve this goal, a multidisciplinary methodology will be used, including whole animal studies using specially designed transgenic mice, in which the expression of the Piezo1 mechanoreceptor can be controlled. In addition, cellular studies will be used to determine physical interaction between Piezo1 and TRPM4 channels by employing fluorescence and imaging techniques, and recordings of electrical signals characteristic of these membrane channels.