New frontier for heart failure treatment

Opening new avenues for the treatment of heart failure, a research has found how the function of a key cardiac protein changes in the case of heart failure.

Since 1976, researchers have known that the heart regulates its calcium sensitivity by phosphorylating (adding negative phosphate groups) to a key cardiac protein called troponin I.

The troponin complex is made up of three proteins, C, I and T which trigger muscle contraction in response to calcium.

In heart failure, the phosphate groups are removed from troponin I but it was not known how this caused an increase in calcium sensitivity.

Assistant professor Peter Hwang and professor Brian Sykes from University of Alberta in Canada studied the troponin complex with nuclear magnetic resonance (NMR) spectroscopy.

They observed that unphosphorylated troponin I binds to troponin C to keep it in an optimal orientation for triggering contraction.

"Scientists till date believed that the dephosphorylation of troponin I seen in heart failure somehow caused the troponin complex to become less functional," Hwang said.

"Actually, the change brings it into the optimal alignment to trigger contraction. The heart has other mechanisms of regulating calcium sensitivity that probably also act by stabilising or disrupting this arrangement," he added.

In calcium sensitivity, calcium ions are pumped in and out of the muscle cell with each heartbeat, turning contractions on and off.

When the calcium sensitivity increases, contractility increases as well; however, the relaxation of the heart becomes slower.

"Both phases of cardiac function are important: impaired contraction leads to systolic heart failure, while impaired relaxation leads to diastolic heart failure. Both types of heart failure are similar in terms of overall prevalence, symptoms and mortality," he said.

Hwang hypothesises that the heart continuously adjusts calcium sensitivity in order to maintain a proper balance between contraction and relaxation.

"A grant by the Heart and Stroke Foundation of Canada is now allowing our team to develop troponin-targeting drugs that modulate calcium sensitivity for the treatment of heart failure. We will see if this hypothesis is correct," Hwang added.

The study appeared in the journal Proceedings of the National Academy of Sciences.