King's College London

In a paper published in JCI Insight, researchers discovered that patients who were on a treatment plan with protease inhibitors to control HIV infection had a build-up of Prelamin A, a protein which has been shown to cause premature ageing of the heart and cardiovascular system. Prelamin A accumulates in heart cells, becomes toxic and causes a strong inflammatory response and premature ageing, effectively injuring the heart and causing it to pump less well.

Using a series of genetic engineering and microscopic techniques, the team from the School of Cardiovascular Medicine & Sciences investigated human and mouse heart tissues to understand the side effects of these drugs.

They found that Prelamin A accumulated in samples from patients with heart disease including HIV-associated heart disease. They also discovered that the accumulation of prelamin A has catastrophic consequences for the integrity of the heart muscle and results in subsequent loss of the heart’s ability to contract.

HIV patients have double the risk of developing cardiovascular disease than non-carriers, therefore the researchers suggest moving to drugs that have fewer side effects such as non-nucleoside reverse transcriptase inhibitors. Although the move to these drugs has been slow, these findings shows that HIV patients should be transitioned to a better combination of therapies quicker, especially if they are beginning to show signs of heart disease. 

The next steps in this research are to investigate whether Prelamin A also builds up in ageing heart tissue and if so, how this can be rectified to reinstate normal processing and normal function of this protein and slow the ageing process.

This research was funded by the British Heart Foundation.

Read the paper here.