January 24, 2011

Research to probe cocaine use, heart drugs links

The effect of HIV/AIDS and its therapy on gene expression is an important aim of the study, which will be carried out using laboratory mice.

Cocaine predisposes users to HIV/AIDS because of risky behavior. It injures the heart and the anti-retroviral medicines used to treat HIV/AIDS also can adversely affect the cardiovascular system, researchers have found. Used together, cocaine and anti-retroviral therapy can amplify the injury from each.

With this in mind, Emory researchers and their colleagues will use a new $5.7 million grant from the National Institute on Drug Abuse of the National Institutes of Health to study the biochemical mechanisms behind cocaine and anti-retroviral drug interactions in mouse models of AIDS.

The effect of HIV/AIDS and its therapy on gene expression is an important aim of the study.

More than 34 million Americans have used cocaine and more than 1.5 million are habitual users, according to estimates. Meanwhile, more than a million Americans are infected with HIV or have full-blown AIDS.

For decades, cocaine has been thought to increase the risk for HIV infection, says cardiac pathologist William Lewis. Lewis is the study's principal investigator and a professor of pathology and laboratory medicine in the School of Medicine.

"HIV/AIDS, along with the use of cocaine and NRTIs [nucleoside reverse transcriptase inhibitors] may lead to cardiomyopathy, a prevalent, life-threatening illness," says Lewis. "Antiretroviral drugs have increased survival rates in those with HIV/AIDS, but unfortunately, these drugs may be cardiotoxic.

"Research from our laboratory and others' has shown that genetic products of HIV, along with antiretroviral drugs, increases cells' oxidative stress, which causes damage to the heart cells, eventually leading to heart failure. Cocaine, HIV/AIDS and antiretroviral nucleosides interact at multiple levels.

"We want to understand which switches are being turned on and which switches are being turned off at the level of the gene. This will enable us to formulate a testable hypothesis on what mechanisms lead to cardiomyopathy and heart failure in AIDS and non-AIDS conditions," Lewis says.

Study researchers include Eva Lee, , Georgia Institute of Technology; Michael Kuhar, School of Medicine and Yerkes National Primate Research Center; and David Harrison, Vanderbilt University.

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