World First Discovery Could Help Reduce Heart Attacks in Women

Victor Chang Cardiac Research Institute

A world first international study is set to change the way we understand heart attacks in women. In Australia, it is estimated that approximately 50,000 women suffer from heart attack or other "acute coronary events" each year.

The collaborative research, spanning three continents and involving more than 15 years of work, compared hundreds of male and female patients with coronary heart disease - the leading cause of heart attack.
In this exciting breakthrough, for the first time scientists were able to apply cutting-edge "systems biology" approaches to pinpoint major molecular and genetic differences arising between men and women at high risk of having a heart attack.
Doctors have long known that women experience different heart attack symptoms to men, with only a third of females experiencing the hallmark crushing chest pain of a typical heart attack often seen in males.

On top of that, women also fare worse after a heart attack due to intrinsic risk factors such as age and diabetes. However, until now, many of the underlying cellular and genetic complexities have remained a mystery.

This new research uncovers a profoundly important aspect of biology that scientists are only now just starting to understand.
The Victor Chang Cardiac Research Institute's Executive Director, Professor Jason Kovacic, is excited to make the announcement and be among the core team of scientists in the groundbreaking study.
"This has blown the doors open and created a whole new way of understanding why coronary disease is different in men and women. The results of this study will lead the way forward to potentially develop more sex-specific medical therapies, and tailored treatments unique to women, down the track." Professor Kovacic said.
The team used these cutting-edge "systems biology" approaches to understand gene interactions – called gene networks.
The fundamental difference the team discovered is that genes that were more active in women with coronary artery disease were strongly associated with cells of the vessel wall, whereas genes more active in men were linked to the immune system.
"When we compared the male and female patients, we saw a huge difference in these genes in smooth muscle cells, which are the most common cells in the wall of the arteries. These are one of the critical cells in causing heart attack," revealed Professor Kovacic.
Importantly, the study also identified new gene networks involved in the development of coronary heart disease.
"A network is a group of hundreds or even thousands of genes that interact with each other. What we actually found was that there are certain networks of genes that are fundamentally different between males and females."
In total, 160 women and 160 men with advanced atherosclerosis of the heart arteries, participated in the comparative study. A range of blood, tissue and cell samples were taken from each patient and used to identify these key gene networks involved in coronary heart disease.
So exciting are the findings, that the paper was fast-tracked to be one of the feature articles in the Fifth Annual Go Red for Women Issue of the scientific journal Çirculation – one of the world's leading journals about the heart.
"We are very excited about this study as it literally opens up a whole new field of research – into networks and how these are different in women versus men - it gives profound insights that weren't there before.
Professor Kovacic said the huge advancements in computer technology and genetic tools over the last two decades has been vital, to show complex pipelines and gene network interactions, that scientists have never before had access to.
The team was led by Hester den Ruijter from Utrecht University, and Johan Björkegren from Mount Sinai Medical Centre in New York and also the Karolinska Institute in Sweden whose STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) bio-bank study underpinned the new data advancement.
"We know that cardiovascular disease is the leading cause of death around the world, and around 50 Australian women have a heart attack every day. So we're really excited about how this study will now be utilized, and where it will progress to next."
"We are now getting a snap-shot look at some of the core mechanisms of the number one killer of society. It's a pretty rare moment when you get profound insights like this," Professor Kovacic said.
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