The agreed project offers an exciting opportunity to support a complementary yet experimentally distinct arm to the current cardiac-related CO research portfolio.
Pioneering work being carried out by researchers at Sheffield Hallam University (SHU) and the University of Leeds is driving critical advances in both the identification of CO-related congenital heart defects, and the aetiology of CO-related cardiac arrythmias in adults respectively.
However, the impact of low-level (≤10ppm) exposure on the complex, highly regulated process of early heart formation in the developing embryo – the extent of which greatly influences cardiac anatomy and physiology later in life – are unknown. Enhanced understanding of how CO impedes normal cardiac development will inform future therapeutic strategies to improve our ability to diagnose, treat and ultimately prevent CO-related mortality and morbidity.
Work by MMU and collaborators (Drs Herigstad, Stafford, and Prof Placzek) has shown that low level CO exposure induces congenital heart defects in the chick embryo (Durrans et al.). This indicates that the process of ‘building’ the embryonic heart has been significantly disrupted.
However, we do not know how, why, or when this occurs. Whilst CORT funded work at SHU will continue to characterize structural defects in vivo, this project will seek to answer the following key questions using a distinct in vitro cell culture-based experimental approach:
- The heart is composed of many different cell types; which cells are affected by exposure to low-levels of CO?
- Cardiac precursor cells carry out specific processes in order to contribute to correct heart formation; how is the behaviour and function of these cells altered in the presence of low level CO?
- The correct timing and integration of these cell functions is imperative for normal heart formation; when are cardiac precursors vulnerable to the effects of low-level CO exposure?
To answer these questions effectively and efficiently, this project will isolate specific types of cardiac precursor cells and grow them in controlled conditions within the lab prior to carrying out experimental investigations.
By removing the cells from the embryonic environment, MMU will MGAPP1 (04/21) reduce potential confounding factors that may obscure the true impact of low-level CO exposure on cells and their behaviours. By identifying which cells are affected, how their functions are impeded, and at what developmental stages these events occur, MMU will form a bedrock of knowledge that will guide future experimental plans and further reveal the extent of low-level CO exposure on foetal cardiovascular health.
