Conference Paper
Differences in extracellular matrix deposition during heart regeneration and scarring in Astyanax mexicanus
Hu, Z., Lemieux, M. and Mommersteeg, M.
Record Number:
4285
Year:
2019
Journal:
AIM 2019
Pages:
37
Abstract:
Heart failure is a global problem affecting 40 million people worldwide and continues to be the
leading cause of global death. Heart failure often develops afer a heart attach, when blockage of
blook flow to the heart leads to oxygen deficiency in the cardiac muscle and irreversible cell death.
In patients fortunate enough to survive a heart attach, the affected heart muscle is replaced by
scar tissue, causing the heart to pump less well, causing heart failure. Scar formation is the main
reparative response in both hearts that can and cannot regenerate after injury and is
characterised by deposition of extracellular matrix (ECM) proteins including elastin, fibronectin,
and divergent isoforms of collagens. The ECM provides an essential physical scaffold for cellular
constituents and initiates bio-chemical and -mechanical cues required for normal tissue functions.
Astyanax mexicanus allows us to directly compare differences in ECM deposition and removal
between a degradable scar in a regenerative setting and a permanent scar in a non-regenerative
setting. Surface-dwelling Astyanax mexicanus can restore their hearts after injury, similar to
zebrafish model, while the cave-dwelling fish from the Pachón cave cannot, similar to the situation
in patients after a heart attack. Using transcriptomics analysis, immunohistochemistry and in situ
hybridisation, we have identified key differences in the scarring response between the surface
and cavefish heart after injury. These differences include ECM proteins (i.e. collagens, laminins,
fibronectin) and their regulators (i.e. mmp9 and mmp13), suggesting properties unique to the
surface fish scar that promote heart regeneration. We will link the key scarring and inflammatory
differences directly to both the genome and the ability for heart regeneration using new and prior
Quantitative Trait Loci analyses. This will allow to find the most fundamental molecular
mechanisms directing the wound healing process towards regeneration versus scarring.
Times Cited:
1
Conference Name:
Astyanax Interrnational Meeting
Relevent Species: