Adrenal gland gene therapy cuts HF risk

Using gene therapy to reduce the adrenal gland’s output of fight or flight hormones could protect against heart failure, US research suggests.

The findings offer a strategy to treat heart failure and help to explain why sympatholytic agents have been unsuccessful in protecting against heart failure.

Currently, beta-blockers are used to inhibit the beta-adrenergic receptors on the heart, blocking the catecholamines that force the heart to work too hard, leading to heart failure.

However, beta-blockers do not reduce the levels of catecholamine produced by the adrenal gland.

By targeting the adrenal gland, the researchers found that they could lower the levels of catecholamine by inhibiting the activity of the regulatory enzyme G-protein-coupled receptor, kinase 2 (GRK2).   

The researchers used mice and rats with chronic heart failure to investigate adrenal signalling and whether enhanced catecholamine caused heart failure.

Real-time polymerase chain reaction was used to show that the levels of mRNA expression for GRK2 were twice as high in the heart failure models compared to the controls.

Catecholamine release was examined from chromaffin cells taken from the adrenal glands. Chromaffin cells from the heart failure models did not inhibit the secretion of catecholamine, but an inhibitory effect was found in the control cells.

The inhibitor beta-adrenergic receptor kinase was used to inhibit GRK2 activity. This resulted in improved myocardial function.

Dr Walter Koch, professor of medicine and director of the centre for translational medicine at Jefferson Medical College, said: ‘If less catecholamine is presented to the heart, the beta receptors destabilise and that improves heart function.’

GRK2 inhibitors could make human gene therapy for heart failure possible, he said.

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