Following heart attacks, adult human hearts form permanent collagen scars. The collagen in these scars is stabilised through a process called cross-linking which enhances stiffening and promotes heart failure.
This project uses imaging probes that report changes in cardiac fibrosis to explore the how novel therapeutics modulate the composition of the scar and improve cardiac function following heart attack.
Challenges
Target discoveryPeople
Organisations
- King's College London
In depth
After a heart attack (myocardial infarction, MI) the heart forms stiff scars made of collagen. These scars are stabilised by strong chemical bonds called cross-links, which make them hard to break down and hinder healing.
Zebrafish hearts, unlike adult human hearts, can regenerate and their scars lack these mature cross-links. Enzymes called lysyl oxidases (LOX/LOXL) create these bonds and are stimulated by TGFβ and BMP family members. High-throughput screening has identified four extracellular inhibitors of the TFGß/BMP family, and these proteins are beneficial when administered after MI.
This project will use molecular MRI probes that selectively report changes in cardiac fibrosis to explore whether inhibitors of TFGß favour cardiac regeneration through inhibition of LOX/LOXL.