The World Health Organization (WHO) reports there are currently about 37 million people infected with HIV. Antiviral drugs can control the progression and prevent the manifestation of AIDS, improving the health and survival rate for patients infected with HIV, but their use has been associated with the development of cardiovascular diseases.
Scientists at the University of Missouri School of Medicine have now discovered an enzyme that can lower the risk of cardiovascular disease caused by these antiviral drugs.
The research study, “Heme Oxygenase-1-Derived Bilirubin Counteracts HIV Protease Inhibitor-Mediated Endothelial Cell Dysfunction,” was published in the journal Free Radical Biology and Medicine.
“The use of antivirals in HIV patients is very important to control the virus, suppress symptoms, and improve quality of life,” the study’s senior author, William Durante, Ph.D., professor of medical pharmacology and physiology at MU School of Medicine, said in a press release. “However, antivirals also are linked to the development of metabolic disorders such as diabetes and obesity, and they are known to increase the risk of cardiovascular disease. Our study focused on protease inhibitors, a very common antiviral used to treat HIV.”
Protease inhibitors can block HIV’s replication and prevent the cellular infection. But these inhibitors also lead to the malfunction of endothelial cells, causing cardiovascular disease.
“Endothelial cells make up the inner lining of blood vessels and are essential to vascular health,” Durante said. “When protease inhibitors are used to treat HIV, endothelial cell function is compromised. The cells’ natural tendency to promote blood flow through the vessel is lost and they also become inflamed. These issues lead to plaque build-up within arteries and, ultimately, cardiovascular disease.”
Durante and his co-workers previously discovered that the protease called heme oxygenase-1 (HO-1) protects against endothelial malfunction. An in vitro model of cultured human endothelial cells allowed the scientists to increase the amount of the protease in the cells.
“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,” Durante said. “HO-1 shows great promise as a defender of endothelial cells in patients being treated for HIV.”
Further studies are however needed to confirm that HO-1 will prevent endothelial cell malfunction with all antiviral drugs. But Durante believes that a better understanding of the enzyme’s role in the reduction of vascular inflammation with protease inhibitors can open a new way for the prevention of cardiovascular disease caused by HIV medication.
The research was financially supported by the National Heart, Lung and Blood Institute of the National Institutes of Health.