Oxford researchers discover novel mechanism that links heart muscle and blood vessel formation

A new pathway that allows cardiac heart muscle to grow with a supporting blood supply has been identified by Oxford Researchers in a study published online in the European Heart Journal.  This may allow novel treatments for the both the failing neonatal and adult heart.

Heart failure is a leading cause of cardiovascular death worldwide and is a major cause of disability. Despite conventional treatments, the outcome has tended to remain poor as the ability to form new heart muscle with a supporting blood supply to keep it viable is limited. In the neonate many congenital heart diseases may give rise to intrinsic heart muscle abnormalities that are difficult to treat. In the adult the commonest cause of heart failure is dead heart muscle secondary to ischaemic heart disease whereby a blockage in a blood vessel causes death of heart muscle.

Researchers selectively deleted a key gene in heart development, Cited2, in just cardiac muscle cells. Lack of this gene very early in development causes major cardiovascular abnormalities, limiting study of its function in cardiac muscle cells themselves. When selective deletion was performed, mice developed particularly thin walled hearts, called non compaction, and ventricular septal defects. Close examination revealed that there was a marked reduction in the number of fine blood vessels seen. The expression of a key vasculogenesis gene Vegf-a, that stimulates small vessel growth, was found to be reduced. Further cell biology experiments showed that Cited2 could actually stimulate Vegf-a production, suggesting heart muscle cell production of Cited2 ensures they grow with a sufficient small blood vessel supply to develop.

Discovery of this pathway suggests important new ways to ensure heart cells grow with a supporting blood vessel network in congenital heart disease and new avenues to repair damaged heart muscle to ensure a well functioning pump.  It is also possible that cancer cells could disrupt this pathway to develop their own blood supply.

The work was funded by the Wellcome Trust and the British Heart Foundation.

Lead researcher said ‘Our study suggests a new pathway that links the formation of cardiac muscle cells to the fine blood vessels they need to survive and work properly.  Learning how this process is coupled and fine tuned may allow possible new exciting cell based therapies to treat heart failure and its considerable morbidity and mortality’.

Professor Shoumo Bhattacharya 

Publication abstract