Understanding how the enzyme NOX4 protects against heart failure

Redox-regulated adaptive pathways in heart failure (renewal)

Researchers at the King’s College London BHF Centre of Research Excellence, led by BHF Professor Ajay Shah have been studying enzymes called NADPH oxidases (NOXs). These enzymes make chemicals – called free radicals – which are considered bad for the heart. In heart failure, the heart enlarges and cannot pump enough blood to meet the body’s demands. It is usually caused by conditions that damage the heart muscle and make it work persistently harder, such as a heart attack, or high blood pressure. The heart muscle responds to the extra workload by remodelling itself. Deciphering how this happens may reveal new ways to treat heart failure. The King’s researchers found that two types of NOX – NOX2 and NOX4 are more active in heart failure. They found that NOX2 is harmful because it promotes muscle thickening and scarring. Unexpectedly the researchers noticed that NOX4 can actually benefit the overworked heart by increasing the blood supply to the heart muscle and improving antioxidant defence pathways. This suggests that blocking NOX2 or boosting NOX4 using drugs could be promising new treatments for heart failure. The BHF have now awarded a grant to the King’s scientists to study this in more detail. They will investigate exactly how free radicals produced by NOX4 protect the heart against failure, by defining the underlying molecular pathways. Drugs that block NOX2 are currently being developed by pharmaceutical companies which means these findings could rapidly move towards the clinic. This latest work investigating NOX4 may reveal another new target for drugs to treat heart failure in the near future.