Heart failure occurs when the heart loses the ability to pump sufficient blood to metabolising tissues, and is the leading cause of death in today’s society. The most common contributing factor of heart failure is cardiac fibrosis, which arises from most cardiovascular pathologies including myocardial infarction (heart attack) and hypertension (high blood pressure). For a pathology that carries such clinical significance, the mechanisms behind cardiac fibrosis are poorly understood. However, secreted signaling factors have been implicated in fibrotic alterations important to the progression of cardiac fibrosis.
Yet our understanding of the mechanisms involved in inter-cellular signaling leading to this fibrotic cardiac pathology remains limited. A major emerging player in intercellular communication is a class of extracellular vesicles (EVs) called exosomes. Exosomes are nano-sized lipid-encapsulated vesicles that contain RNA and proteins which can mediate intercellular signalling to elicit a functional response. Although exosomes are established to activate fibrotic processes, their role in the development of cardiac fibrosis remains poorly understood. Here, we aim to investigate the signals released from fibrotic cardiac tissue, as well as establish the role of exosomes (and other types of EVs) during the development of in vivo and in vitro models of cardiac fibrosis.
To achieve this, we will employ “state-of-the-art” high-resolution mass spectrometry and preclinical mouse models of myocardial infarction and hypertension. This will help define the cargo of exosomes and mechanisms which temporally regulate the progression of cardiac fibrosis. Importantly, this will help identify likely contributors of disease pathology which can guide design of novel nano-based therapeutics.