Molecule hope for blocked arteries

By MICHAEL OTTO

Researchers at the University of Auckland have discovered a way to modify blood vessels that could eventually help prevent heart attacks.

In experiments with rat arteries, Associate Professor Mervyn Merrilees and his team at the School of Medicine's anatomy department have replaced a large molecule called versican, which binds with soluble cholesterol to form deposits in vessel walls, with a non-binding smaller version.

The researchers now need ethical approval to extend their experiments to human blood vessels, using hearts obtained from heart transplant operations.

"We're excited by what we have found because we think it has considerable potential," said Professor Merrilees.

"[But] we are also very cautious about extrapolating results too far."

Cholesterol deposits accumulating in coronary artery walls are a significant heart disease risk factor.

Heart attacks occur when thickened coronary arteries contain lesions that make the vessel wall unstable and likely to fissure or crack, leading to a blood clot which blocks the artery.

Coronary heart disease is a leading cause of death, killing 23 per cent of New Zealanders, according to the Heart Foundation.

The research involved seeding blood vessel walls with cells that had been genetically altered to produce the smaller versican molecule.

The larger version of versican is shaped like a bottle brush with handles at each end.

The negatively charged sugar chains, which form the bristles of the brush, bind with the positively charged outer protein covering of cholesterol. The combination then accumulates in artery walls, which become thickened.

But the small version of the molecule has no chains, so does not bind with cholesterol.

"Even partially removing [large] versican may be sufficient to tip the balance in favour of less trapping of cholesterol," said Professor Merrilees.

Professor Merrilees' team also found that introducing the small form of versican resulted in a marked increase in elastic fibres in rat blood vessel cells, making the vessels more flexible and less prone to fracturing.

"The loss of elastin in many organs with age, notably in vessels, skin and lungs, is a problem and the ability to restore elastin could conceivably have significant benefits," said Professor Merrilees.

He hoped the gene therapy would one day lead to the development of a drug which promoted the smaller molecule.

Similar techniques might one day be used in skin grafts, plastic surgery and growing vessels for vascular operations.


How it works

A major risk factor in heart disease is the build-up of cholesterol deposits in blood vessel walls.

Many deposits occur because a large molecule, called versican, binds with soluble cholesterol.

Auckland University researchers have replaced this large molecule with a smaller, non-binding version.

The technique worked on rats but has not yet been tried on humans.