2019 Cardiac Mechano-signaling Update

Cardiac mechano-signaling (CMS) Research Update

12 August 2019

The heart is a companion we must rely on 24/7, all our life. It cannot rest, and keeps our blood flow going. This incredible organ stoically transforms electrical into chemical and finally, mechanical signals, ultimately cycling between filling and pumping sequences, like a piston pump. It has to react to changes in load and blood demand, e.g. in exercise and heavy work. Thus, the workload must also be sensed in terms of sensing the mechanical strain on the heart walls and each heart cell reacts with signal modulations. Some of these cellular mechanical biosensors comprise mechanosensitive ion channels (MSC) on the surface membrane of cardiomyocytes (CMs) that are supposed to open in response to wall strain to allow Ca²⁺ influx into CMs, to not only modulate electrical activity and chemical signalling, but also to support growth and cell anchorage during our life.

Under disease conditions, in particular with the very common condition of cardiac hypertrophy and heart failure in Australia, the heart is exposed to reduced pumping force, resulting in increased residual filling pressure and thus, aberrant activation of MSC and downstream signalling. Thus, to control the MSC activity in disease would represent a new tool to control heart failure. Development of the MultiStretcher platform in this project presents a significant step in this direction.

In our project, we will study responses of cardiac model cells to define strains pulling individual cells in multiple directions applying a novel biomechatronics ‘stretch rack’ systems technology that will be re-engineered for high throughput/content application to NSW cardiac research. This international Australian-German partnership will contribute to NSW’s capacity building for better understanding the underlying causes of CVD and their prevention/treatment in the future that, in particular, will benefit adult males and females living in the lowest socioeconomic areas. We will determine the crucial involvement of a specific type of MSC, called Piezo1, in driving aberrant heart signals in response to overstretch of heart cells and will employ pharmacological agents to control this mechanical biosensor.

We expect our fundamental research, which combines cardiac research, biophysics and biotechnology, will be applied to clinical settings using human cells as a validation after completion of our project, resulting in translation of pharmacology insights into drug development pipelines. We will disseminate our research findings though publications in high-impact international scientific journals and presentations at national and international meetings.

*This project was supported by the NSW Government's Cardiovascular Research Capacity Building Program.

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