LISA CASSIS: The leading cause of death in women is coronary artery disease by far. But
having said that, women develop coronary artery disease almost 10 years later than men. Now
for many, many years, research focused on sex hormones, like estrogen and progesterone,
as contributors to why women might be protected and then why, after menopause, they might
have more risk. And there is a lot to be said and a lot of evidence that estrogen is indeed
protective against coronary artery disease and also promotes a more favorable lipid profile--so
good lipids rather than bad lipids.
YASIR AL-SIRAJ: circulating lipids are fat molecules that are transported by the blood.
But if they are too high, they will start to accumulate in and on the wall of the artery.
And that accumulation will lead to building up plaques. These plaques hardens and narrows
the artery, and this will lead to reduced amount of blood flow to the vital organs.
And this is what's called atherosclerosis.
LISA CASSIS: And it sets into play a lot of inflammation and other processes that can
then give you ultimately a heart attack. There are two major ways you make these lipids.
You absorb them from your diet. Or you make them in your liver. So we looked at both of
those as how our X sex chromosomes were influencing the levels of lipids in the blood and in the
arteries.
And what we found is that actually an XX sex chromosome complement pretty much sets you
totally into place to efficiently use fat. What our hypothesis would suggest is that
we have evolved to be very efficient at absorbing and storing fat as women. We need it for childbearing
purposes. We're mothers. We feed babies. We're set up, potentially through our XX sex chromosomes,
to make us effectively absorb that lipid from the diet and put it into our fat cells and
maybe even make it in the liver. Now, we're OK because estrogen is protecting us from
getting it into the arteries and getting trapped there. But once we go through menopause and
those levels of those sex hormones decline, then all we have, this is our hypothesis,
is that XX, thrifty, fat absorbing kind of genotype.
YASIR AL-SIRAJ: we found that the presence of two X chromosomes increase the circulating
lipids and atherosclerosis in mice. We believe that results from our studies provide
important information to clinical care because this suggests that the female gonadal hormones,
like estrogens, are unlikely to be the only determinants of the sex differences to the
risk of coronary artery disease. So that means that there is another determinant of
the sex differences-- basically, its genetic components, specifically genes on the sex
chromosomes. And that could lead to the development of sex-specific therapy that could work in
one sex, but not in the other. Well, the next step in this research, we are
going to study the role of number of X chromosomes in atherosclerosis because the results from
these studies, we don't know if it's due to the presence of two X chromosomes or due to
the absence of the Y chromosome.
LISA CASSIS: we're looking at genes that are changed in the liver and in the intestine.
We're trying to find those targets. What kind of a target relates to serum lipids and atherosclerosis
that might be a novel target that we haven't thought about before that we could then go
after with either an available drug or creating a new drug for that purpose? We may also use
this information to guide women on the choice of their diet. For example, if they're very
effective fat absorbers, obviously, once they get postmenopausal, they need to be careful
about the fat content. It might drive certain types of diets, depending on your age and
your menopausal status. And I guess one of the exciting things for me is there are others
that are studying this sort of area. But there are not that many in the cardiovascular system.
So I'm excited because I think we have, with our tools and our knowledge, maybe a very
defined path to get at, how we can use this information to drive therapy and prevent disease.