Attacking heart attacks

A FUNGUS, Aspergillus fumigatus, which can kill people with damaged immune systems, has provided an important weapon for fighting against coronary heart disease (CHD), according to researchers from Tokyo's Kitasato University. They found that a previously unknown group of compounds produced by this fungus can block an enzyme responsible for the buildup of cholesterol in arteries.

Aspergillus fumigatus is harmless for healthy people. But in patients with impaired immune systems, like those suffering from aids, it infects the lungs and causes aspergillosis, which is usually fatal. This fungus has been reported to be an increasingly important cause of death in people on immunosuppresants, like thalassaemics. But this fungus, says Satoshi Omura of Kitasato University, holds the promise of developing a new class of drugs which can control the way the body absorbs cholesterol, thereby minimising the risk of heart attacks caused by the narrowing of arteries.

The Japanese group was looking for new drugs that could block an enzyme -- cholesterol acyltransferase (ACAT) -- believed to be involved in several processes which cause atheroscleroris, cholesterol buildup inside blood vessels.

Scientists believe that ACAT increases the absorption of dietary cholesterol from the gut and its accumulation throughout the body. "So if acat could be blocked, the amount of cholesterol entering the bloodstream would be decreased, thus reducing the cholesterol buildup in blood vessels," argues Omura.

Researchers found a particular strain of Aspergillus fumigatus from a soil sample from the Shinjuku area of Tokyo, from which they successfully isolated a group of previously unknown compounds, which they named pyripyropenes. "These compounds have proved to be the most active naturally occurring inhibitors of acat ever discovered. A single dose has been found to reduce blood cholesterol levels in hamsters by nearly 50 per cent," explains Omura.

Using a variant of the magnetic resonance pectroscopy technique -- a process which can help determine a molecule's structure by analysing the behaviour of its constitutent atoms in a powerful magnetic field -- the Japanese research group, in collaboration with an international team led by Amos Smith of the University of Pennsylvania, have worked out the relative positions of each atom in a pyripyropene molecule. "This would help to form the basis of drugs that can be designed to treat atherosclerosis," says Omura.