A new study has demonstrated how the enzyme heme oxygenase-1 (HO-1) could protect HIV patients receiving protease inhibitor (PI) treatment from developing cardiovascular disease.
Antivirals are commonly used in treating HIV and halt the virus from progressing to AIDS. However, PIs have been linked to serious adverse events including cardiovascular disease. They can damage the endothelial cells, which promote blood flow through vessels, and this damage can lead to plaque build-up and ultimately, cardiovascular disease.
The researchers tested three different PIs: ritonavir, atazanavir, and lopinavir. They each stimulated the expression of HO-1 protein and mRNA, this induction of HO-1 was tied to an increase in NF-E2-related factor-2 (Nrf2) activity and reactive oxygen species (ROS).
The study researchers tested the endothelial-protective enzyme, HO-1, by increasing its amount in a cell-based model of cultured human endothelial cells. They found that the induction of HO-1 counteracted the anti-proliferative and inflammatory actions of PIs on endothelial cells by generating bilirubin.
“Increasing the presence of HO-1 in our model before exposing it to a protease inhibitor allowed the medication to do its job without causing endothelial dysfunction,” said William Durante, PhD, professor at MU School of Medicine, and lead author of the study.
The findings of the study, which was published in Free Radical Biology and Medicine, could be the instigator for the development of future treatments that counteract the negative vascular impacts of antivirals. After acknowledging that more research is needed to verify if HO-1 will prevent endothelial cell dysfunction with all antiviral medications, Durante said, “HO-1 shows great promise as a defender of endothelial cells in patients being treated for HIV.”
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