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New genetic study unlocks the causes of why our arteries harden

Victor Chang Cardiac Research Institute 2 mins read
Professor Jason Kovacic

An international team of scientists has analysed data from more than 35,000 people and identified 11 genes that contribute to the hardening of the heart’s arteries.

It’s hoped the findings will lead the way for new treatments that could help prevent coronary heart disease – the leading cause of death in Australia and biggest driver of heart attacks.

One of the study’s authors Professor Jason Kovacic, CEO and Director of the Victor Chang Cardiac Research Institute, says understanding the biological mechanisms was a big step forward.

“Coronary heart disease is by far the most common heart disease affecting Australians. It is the biggest driver of heart attacks so if we can get in early and stop its progression in the first place, we could save tens of thousands of lives each year,” says Professor Kovacic.

The process that causes the coronary arteries to harden is due to the build-up of calcium in these arteries and it can take place over many years. It is caused by a buildup of fatty plaque which eventually hardens/calcifies, causing the arteries to narrow.

This can affect the heart’s ability to pump blood, oxygen, and nutrients around the body and can cause a heart attack if a piece of the calcified plaque breaks off.

The study was led by Dr Clint Miller from the University of Virginia and was published in Nature Genetics. This was the largest such “meta-analysis” yet conducted to understand the genetic basis of coronary artery calcification. Unlike many medical studies, it contained a large proportion of participants of non-Caucasian backgrounds, including 8,867 individuals of African ancestry.

The team identified 11 genes, eight of which were new, and the role they played in coronary artery calcification.

To validate their findings, the researchers conducted gene queries and experimental studies in human coronary artery tissues and smooth muscle cells and demonstrated direct effects on calcification and related cellular processes.

The study also confirmed that another gene called PHACTR1 plays a big role in the calcification process.

PHACTR1 is currently being studied by Professor Kovacic’s team at the Institute’s headquarters in Sydney and it is also known to be a major driver of SCAD heart attacks and fibromuscular dysplasia.

Scientists can now work to develop drugs or repurpose existing ones that can target the genes or encoded proteins to modulate the calcification process.

While additional research needs to be done to determine how best to target these genes and affected pathways, the new discoveries could set the stage for improved risk stratification or early interventions that prevent the progression of coronary heart disease before it can take hold. That would be a game-changer for treating a disease responsible for more than 17 million deaths annually around the world.

A link to the full study in Nature Genetics is available here.


Key Facts:

Coronary heart disease caused the deaths of 18712 Australians in 2022 

Coronary heart disease was the leading cause of death in Australia in 2022. 

 

Contact details:

Julia Timms

j.timms@victorchang.edu.au

0457 517355

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