An Australian scientist has led landmark research that has the potential to stop arteries of the heart from becoming clogged. It shows that a particular gene allows plaques of fat and cholesterol to build up in the arteries.

“It’s possible to make a drug to deactivate this gene,” said Jason Kovacic, the executive director of Sydney’s Victor Chang Cardiac Research Institute.

He said there were drugs that could do this now, but they would be blunt instruments with too many side-effects.

These drugs are currently used to treat various cancers and would need to be sharpened so that they specifically targeted the gene and its effects on cells that form the lining of the heart arteries.

The fact that they exist and have been widely used would likely take at least five years off the development process of a new generation of therapies to target blood vessels.

“Cells that line the blood vessels play an incredibly important role in heart health. We’ve known for some time that there is a switch that turns these cells from being healthy to ones that drive the build-up of plaque,” Professor Kovacic said.

“After six years of research, we’ve been able to identify a key gene that controls this process, understand how it works and take a step closer to silencing it, blocking its ability from turning on in the first place.”

One in four deaths

When plaque builds up in arteries, a person has atherosclerosis. When plaque breaks away, it can form blood clots that, in turn, cause heart attacks.

“Every year millions of people die from the consequences of atherosclerosis. Drugs like statins help, but if we could stop this disease from occurring, that would be transformative in the treatment of heart disease.”

More than one in four deaths in Australia in 2018 were due to cardiovascular diseases, making it the leading cause of death in the country. And then there are millions who recover and live with the legacy of the disease.

The gene at the centre of this research is called histone deacetylase 9, or HDAC9. Several cancer drugs work on HDAC molecules in general, but because they are fairly non-selective, they tend to have a lot of side-effects. A more targeted approach is now needed.

When Professor Kovacic returned home to Australia in March 2020, he continued to run two nodes of his laboratory: one in Sydney and one at the Icahn School of Medicine at Mount Sinai in New York.

This research was based in New York, and was funded by the US National Institutes of Health, and involved an international team from the US and Europe.

There was another Australian in the team too. Dr Laura Lecce, a former postdoctoral researcher in the Kovacic Lab at Mount Sinai is the co-first author of the paper.

The research was published on Tuesday in the Journal of Clinical Investigation, which traditionally publishes studies that show major breakthroughs that have a clear line of sight to the clinic.

“At the individual level, different things cause atherosclerosis, such as high cholesterol, high blood pressure, smoking and diabetes. They all have a slightly different mechanism but this one crucial component, in the lining of the blood vessels, is key to this process,” Professor Kovacic said.

The study used cell lines derived from human cells of the arteries to the heart. “They were the exact cells where this problem is most critical and mirror the situation where heart attack can occur,” he said.

The research reflects The Victor Chang Institute growing to become an international force in fighting cardiovascular disease.

This article was originally posted on The Australian Financial Review here.

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