The Female Heart

The female heart has been vastly understudied. Naomi Chesler is a leader in researching the female heart and how sex hormones like estrogen affect the heart's function. Her research is helping prevent heart failure in women and men.

Naomi Chesler is a UC Irvine professor of biomedical engineering and the director of UC Irvine's Edwards Life Sciences Foundation Cardiovascular Innovation and Research Center.

Transcript:

[Sound: Heartbeat of Emily Hope, Wikimedia Commons]

NATALIE TSO, HOST: That is the heartbeat from a woman named Emily.

[Sci fi music]

Women's hearts have been historically understudied, and that is a loss not only for women, but men too as the female hormone estrogen could be useful in protecting the heart. Naomi Chesler is a leader in studying female hearts. She is a UC Irvine professor of biomedical engineering and the director of UC Irvine's Edwards Life Sciences Foundation Cardiovascular Innovation and Research Center.

She discovered an important contributor to heart failure in women. What got her interested in biomedical engineering?

NAOMI CHESLER: When I was a kid, I really enjoyed watching The Six Million Dollar Man, and that was very inspirational for me. I really loved the idea that we could rebuild people and make them stronger. I was also really good at math and science, and I was told when I was a kid that being an engineer was a way to be really creative, using math and science.

So then engineering became really appealing to me. I got into the heart because I felt like, you know, we can argue with neuroscientists about this, but I thought it was the most important organ in the body that, you know, you can't really live without a functional heart. And it was a very exciting organ to me. It's got complex mechanical properties and electrical properties, and it drives blood flow that supplies nutrients and oxygen to every cell and tissue in your body. I think that's why I was so intrigued with it.

TSO: So why have female hearts been largely understudied?

CHESLER: Generations of scientists have been largely male, and those generations of scientists have considered the male the standard and just assume that women would be similar or just a smaller version, the way that folks often assume that children are a smaller version of adults, which is really a very bad assumption.

They're very different physiologically, psychologically, you know, hormonal, like just almost in every way. They're not just small adults. And similarly, women are not just small men.

TSO: She studies the aspects of the heart that most scientists don't. Right heart failure due to pulmonary hypertension, also known as high blood pressure in the arteries of the lungs.

CHESLER: Actually, pulmonary arterial hypertension, which is sort of the analog to systemic hypertension, which is very common, affects four times more women than men and used to be deadly within two to three years and also affect women in their 30s.

So here was this disease that affected young women in their reproductive period and was like very quickly deadly. And we knew very little about it. So I started looking at pulmonary hypertension. And as an engineer, I recognized that when arteries are subjected to high pressure for long periods of time, they typically stiffen. And we knew this to be true about the systemic circulation.

And I asked the question whether that was true about the pulmonary circulation. And I proved that it was. And I got a lot of “So whats” like “So what if the pulmonary arteries stiffen? The big deal is that the resistance increases.” And it wasn't until a couple of years after I published my findings that a clinical team showed that pulmonary artery stiffness was a better predictor of mortality from pulmonary hypertension than resistance, that people started paying attention.

TSO: Chesler’s contribution was key to understanding right heart failure.

CHESLER : And now permanent artery stiffness is measured quite frequently in clinical communities, and it's more well recognized that it's a really important contributor to right heart failure.

TSO: Roughly 400,000 deaths each year are caused by heart failure in the US, and 15 to 24% of those deaths are due to right heart failure.

Now, what is different about the female heart?

CHESLER: So the female heart is smaller for sure. Actually, our most recent study shows that in rats there are changes in contractility over the estrous cycle, which is the rat equivalent of a menstrual cycle. I guess that's another reason why females have been excluded from a lot of scientific studies is that any kind of variation in any kind of function over the normal hormonal cycling is considered a source of error or variation.

[Sound: EKG]

TSO: That's an echocardiogram or EKG.

CHESLER: That is the sound of

Episode Transcript

[Sound (00:01):
Heartbeat of Emily Hope] NATALIE TSO, HOST: That is the heartbeat from a woman named Emily.
[Sci fi music] Women's hearts have been historically understudied,and that is a loss not only for women,
but men tooas the female hormone estrogen could be useful in protecting the heart.
Naomi Chesler is a leader in studying female hearts.

(00:21):
She is a UC Irvine professor of biomedical engineeringand the director of UC Irvine's Edwards Life Sciences
Foundation Cardiovascular Innovation and Research Center.
She discovered an important contributor to heart failure in women.
What got her interested in biomedical engineering?

NAOMI CHESLER (00:39):
When I was a kid, I really enjoyed watching The Six Million Dollar Man, and that was very inspirational for me.
I really loved the idea that we could rebuild peopleand make them stronger.
I was also really good at math and science, and I was toldwhen I was a kid that being an engineer was a way to be really creative,
using math and science.So then engineering became really appealing to me.

(01:01):
I got into the heart because I felt like,you know, we can argue with neuroscientists about this,
but I thought it was the most important organ in the bodythat, you know, you can't really live without a functional heart.
And it was a very exciting organ to me.
It's got complex mechanical properties and electrical properties,and it drives blood flow

(01:25):
that supplies nutrients and oxygento every cell and tissue in your body.
I think that's why I was so intrigued with it.

TSO (01:34):
So why have female hearts been largely understudied?

CHESLER (01:37):
Generations of scientists have been largely male, and those generations of scientists have considered
the male the standard and just assume that women would be similaror just a smaller version,
the way that folks often assume that childrenare a smaller version of adults, which is really a very bad assumption.

(02:00):
They're very different physiologically, psychologically,you know, hormonal, like just almost in every way.
They're not just small adults.And similarly, women are not just small men.

TSO (02:10):
She studies the aspects of the heart that most scientists don't.
Right heart failure due to pulmonary hypertension,also known as high blood pressure in the arteries of the lungs.

CHESLER (02:22):
Actually, pulmonary arterial hypertension, which is sort of the analog to systemic hypertension,
which is very common,
affects four times more women than men and used to be deadlywithin two to three years and also affect women in their 30s.
So here was this disease that affected young womenin their reproductive period and was like very quickly deadly.

(02:48):
And we knew very little about it.So I started looking at pulmonary hypertension.
And as an engineer, I recognized that when arteries are subjectedto high pressure for long periods of time, they typically stiffen.
And we knew this to be true about the systemic circulation.
And I asked the questionwhether that was true about the pulmonary circulation.
And I proved that it was.
And I got a lot of “So whats” like “Sowhat if the pulmonary arteries stiffen?

(03:14):
The big deal is that the resistance increases.”And it wasn't until a couple of years after I published my findings
that a clinical team showed that pulmonary arterystiffness was a better predictor of mortality
from pulmonary hypertension than resistance,that people started paying attention.

TSO (03:34):
Chesler’s contribution was key to understanding right heart failure.

CHESLER (03:38):
And now permanent artery stiffness is measured
quite frequently in clinical communities, and it's more well recognizedthat it's a really important contributor to right heart failure.

TSO (03:48):
Roughly 400,000 deaths each year are caused by heart failure in the US, and 15 to 24% of those deaths are due to right heart failure.

Now, what is different about the female heart? CHESLER: So the female heart is smaller for sure. (03:58):
undefined
Actually, our most recent study shows that in rats there are changes
in contractility over the estrous cycle,which is the rat equivalent of a menstrual cycle.
I guess that's another reason why females have been excludedfrom a lot of scientific studies is that any kind of variation

(04:23):
in any kind of function over the normal hormonal cyclingis considered a source of error or variation.

[SOUND (04:31):
EKG] TSO

CHESLER: That is the sound of flow through the tricuspid valve in a mouse heart. (04:35):
undefined
That's the kind of signal that we analyze to see
how the heart is functioning, to see whether the heart functions betteror worse with the loss of estrogen.
Biomedical engineering graduate student Partima Prabala

(04:56):
tells us what they found in animal models with less estrogen.

PARTIMA PRABALA (05:00):
We're seeing that when there's a depletion of estrogen in the rats that have been oophorectomized, so they have their ovaries
removed, there's a more exacerbated phenotype of HFpEFwhich is what we would expect because estrogen is cardioprotective.

[Sci fi music] TSO (05:13):
HFpEF is heart failure with preserved ejection fraction,
or when the heart squeezes normallybut becomes too stiff to relax and fill with enough blood between beats.
The team found that in rats, it's more pronouncedwhen there's less estrogen.

CHESLER (05:28):
Estrogen is a very potent signal in the body in all sorts of ways, and it's involved in a number of different signaling mechanisms.
Loss of estrogen or estrogen deficiency is certainly a very importantphysiological stimulus, let's say, for heart changes.
So what do we want to do?
We want to understand how is it that loss of estrogenpredisposes to heart failure with preserved ejection fraction

(05:53):
and if we can find a protective pathway through which estrogen acts,it could be available to both men and women.
Now we are not going to go giving out estrogen — that has actuallybeen tried or the estrogen mimics — that's not successful.
So we have to find the mechanismand then go upstream of the estrogen pathway and go to the direct
agent that is offering cardiovascular protectionand provide a therapy based on that mechanism.

[Sound of Emily Hope’s heartbeat] TSO (06:20):
Chesler’s groundbreaking work studying sex differences and the influence of sex hormones on heart
functions could lead to better treatmentand prevention of heart failure in both women and men.
The Lab Beat is brought to you by the UC IrvineSamueli School of Engineering, and I'm Natalie Tso.
Thanks for joining me, and we'll see you at the next cutting-edge lab.