Arteries may be vulnerable to HIV attack

Until the mid-1990s, with the advent of the antiviral drugs known as protease inhibitors, investigators paid relatively little attention to the long-term effects of an HIV infection. After all, most people harboring the virus died of AIDS within a few years after diagnosis.

Now that HIV-infected people are living longer, however, their medical histories hint that they face an increased risk of coronary-artery disease.

While some researchers attribute this to side effects of the antiviral drugs, a new study indicates that HIV directly interacts with artery cells and may thereby predispose infected people to heart attacks.

Last year, cardiologist Alison D. Schecter of the Mount Sinai School of Medicine in New York and her colleagues reported that smooth muscle cells, a major component of arterial cell walls, make a surface protein called CCR5. This finding was unexpected, says Schecter, because scientists thought that only white blood cells sport CCR5. It enables these immune cells to respond to chemicals called chemokines.

Although it’s classified as a chemokine receptor, CCR5 also serves an infamous function. Several years ago, scientists found that HIV infects immune cells by first latching onto CCR5, or similar chemokine receptors, and another immune-cell surface protein called CD4 (SN: 6/22/96, p. 390:

Smooth muscle cells also make CD4, as well as another chemokine receptor that the AIDS virus can exploit, Schecter and her colleagues now report in the Aug. 28 Proceedings of the National Academy of Sciences. Moreover, the scientists describe test-tube experiments in which they expose smooth muscle cells to gp120, the protein that makes up HIV’s outer envelope. The cells respond by making tissue factor, a protein that helps trigger the clotting of blood.

These findings suggest that HIV’s interaction with smooth muscle cells may bring about blockages in coronary arteries or worsen preexisting ones, says Schecter.

This paper is “an important contribution in terms of postulating a mechanism for how HIV may impact on coronary artery disease,” notes Marshall J. Glesby of the Weill Medical College of Cornell University in New York. He recently coauthored a review of the links between heart disease and the AIDS virus.

Glesby isn’t yet convinced that coronary artery disease is unusually prevalent in HIV-infected people. Ongoing studies should soon resolve that issue, he adds.

Schecter and Glesby agree that the new work doesn’t challenge the notion that antiviral drugs may also promote coronary artery disease. Protease inhibitors, for example, alter the amounts and kinds of lipids in the blood, which directly affect heart attack risk.

Still, there have been enough reports of heart attacks in HIV-infected people not taking protease inhibitors for researchers to wonder if the virus itself is to blame, says Schecter. Her group now plans to observe what happens when smooth muscle cells are exposed to HIV itself, instead of to just one of its envelope proteins.

A recent report by an Italian group suggests that HIV can infect arterial smooth muscle cells, Schecter notes. Even if the AIDS virus doesn’t get into those cells, HIV’s contact with CCR5 and CD4 may stimulate them in unhealthy ways, she says.

Beyond revealing another way that HIV may harm its host, the new findings imply that smooth muscle cells have unappreciated complexity. Schecter and her team have launched investigations into the arterial-cell function of CD4, CCR5, and other molecules known to mediate the body’s immune response.

The arteries’ “smooth muscle cells have the stigma of just being structural support [cells] that respond to growth factors, but I think we’re finding they can do a lot more,” says Schecter. “We like to think of smooth muscle cells as immunological mediators in the [blood] vessel wall.”

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