Although individuals who are HIV positive can now live longer because of potent anti-retroviral drugs, their rate of cardiovascular disease has increased dramatically. Doctors have been studying whether the increase comes from the drugs used to treat the virus or from the infection itself.
Now, researchers at Emory University have shown in an animal model that the presence of HIV proteins, without a replicating virus, impairs blood vessel function. They also show that they can reverse the effects of the HIV proteins with antioxidant dietary supplements.
The team’s results are published online and scheduled for publication in the June edition of the American Journal of Physiology, Heart and Circulatory Physiology.
"Our work suggests that HIV-1 proteins, by themselves, cause oxidative stress and can affect cardiovascular function," says Roy Sutliff, PhD, assistant professor of medicine (pulmonary, allergy and critical care) at Emory University School of Medicine.
Oxidative stress means an abundance of reactive oxygen species, harmful oxygen-containing molecules that interfere with relaxation of blood vessels and trigger the formation of lesions leading to heart attack and stroke.
Sutliff and his colleagues, who are based at the Atlanta Veterans Affairs Medical Center, studied rats that have an HIV virus that can’t replicate incorporated into their DNA. The virus does not kill white blood cells as it does in human patients, but parts of the virus show up in the rats’ blood and lung fluid.
The team found that the genetically modified rats have less nitric oxide in the linings of their aortas, the main artery leaving the heart. Nitric oxide is a short-lived messenger that tells the smooth muscle around blood vessels to relax. Oxidative stress can reduce the levels of nitric oxide and inhibit blood vessel relaxation, Sutliff says.
The authors found that they could reverse the signs of oxidative stress and restore blood vessel relaxation in the rats by giving them procysteine, which stimulates the production of glutathione, a natural antioxidant.
Some people who are HIV positive take similar dietary supplements, such as n-acetyl cysteine, with the aim of improving immune function and reducing oxidative stress. However, Sutliff cautions that the clinical data on the benefits of n-acetyl cysteine on cardiovascular disease in HIV-positive patients is mixed.
"Our main finding is that the oxidative stress that comes from HIV-1 proteins is distinct from the effects of anti-retroviral therapy or the activation of the immune system that comes from fighting a replicating virus," he says.
The paper’s first author is Erik R. Kline, PhD, with contributions from research specialists Dean Kleinhenz and Bill Liang, and from faculty Sergey Dikalov, PhD, David Guidot, MD, Mike Hart, MD, and Dean Jones, PhD, in the Department of Medicine, Emory University School of Medicine.
The research was funded by the National Institutes of Health.