Why do women have lower rates of heart failure than men for most of their lives?
University of Guelph researchers have uncovered a possible clue - an actin binding protein called "CapZ" that also protects against heart attacks.
Now they'll be studying how its levels are affected by gender and aging, backed by a prestigious Catalyst Grant from the Canadian Institutes of Health Research (CIHR).
Their research may lead to new therapeutic treatments for reducing heart problems and extending lives of both men and women.
"Age continues to be the largest independent risk factor for the development of heart failure," said Glen Pyle, a professor in the Department of Biomedical Sciences in the Ontario Veterinary College and member of U of G's Centre for Cardiovascular Investigations.
"With people living longer throughout the world, it's expected that the rates of heart failure will rise dramatically."
Pre-menopausal women are relatively protected against heart failure compared to men, Pyle said. But the gap starts to close after menopause; by age 80, women and men are at equal risk. No one knows exactly why.
It's been speculated that estrogen plays a role, "but what are the hormonal changes doing to the cells in the heart? That is where we don't know very much," Pyle said.
"Once we figure it out, we can identify what is happening after menopause to make females more vulnerable to heart failure, and why they are protected earlier in life."
Previously, Pyle found that hearts of aged male mice contain higher levels of CapZ than female mice of the same age. The males show signs of declining heart performance, but the females have normal function.
Pyle's group has discovered that female mice somehow decrease CapZ levels to protect against cardiac dysfunction, while male mice are unable to do so.
Pyle and his research team genetically engineered male mice with decreased CapZ levels, and found it prevented heart failure.
"Even a small decrease - 20 per cent - offered protection," he said.
"These results suggest that CapZ may be a viable target to protect hearts against the process of aging."
He now plans to assess the impact of sex and aging on CapZ levels in the heart.
"We'll be looking at how and when protein levels naturally change over time in both female and male mice," said Pyle, who has studied CapZ for nearly 20 years.
They will need to study mice much older than those typically used in research - two and three years of age, the equivalent of 70 and 90 years in humans.
Nurturing lab mice to that age takes time and resources. That is why the $150,000 CIHR Catalyst Grant is critical, Pyle said. The funding comes from CIHR's Institute of Cancer Research, Institute of Genetics, Institute of Infection and Immunity, and Institute of Gender and Health.
"We plan to age the female mice longer, to three years — the equivalent of 90 years in humans — to see when they get to the point where they lose the CapZ protection," he said.
This is important because menopause duration varies in women, and it takes time for the heart to change. "We often do not see an effect in women until they are in their 60s or 70s," Pyle said.
Pyle will work with postdoctoral researcher Ilka Lorenzen-Schmidt on the project, which he called "unique research and in an under-examined field."
"The relative lack of research using female subjects is finally being recognized as a significant issue in medicine, and aging populations worldwide are creating the potential for a heart failure epidemic," he said.
"This work will advance our understanding of the influence of both gender and aging on heart function, and tackle two emerging problems at the same time."
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