Investigating the role of the TWIST1 gene in atherosclerosis

Role of the transcription factor twist1 in endothelial pathophysiology and atherosclerosis progression (renewal)

Atherosclerosis is the leading cause of death worldwide. It causes fatty deposits called plaques to build-up beneath the inner lining of arteries (the endothelium). If a plaque bursts, it can cause a blood clot to form. This can block the blood supply to parts of the heart or brain tissue, resulting in a heart attack or stroke. Recent studies found that people with diseased arteries are more likely to have a change in activation of a gene called TWIST1. However, the biology that underpins this link between gene and disease is unknown. A team of researchers led by Professor Paul Evans at the University of Sheffield found that high levels of TWIST1 protein are produced in the inner walls of diseased arteries. They also discovered that TWIST1 is triggered by sluggish blood flow (a contributing factor in the development of plaques) and switches on disease-causing genes. Professor Evans and his team will now investigate the precise ways in which TWIST1 contributes to the development of dangerous plaques that can cause catastrophic heart attacks and strokes. Researchers will study arteries from mice and humans to determine if genetic changes, or mutations, of TWIST1 alter the behaviour of the endothelium. They will also target TWIST1 with therapeutic nanoparticles to see if they can slow the progression of plaques. This research could identify new drug targets and treatment strategies for atherosclerosis.