Have you heard of the inherited heart condition that affects about 1 in 500 people?

It’s called hypertrophic cardiomyopathyand it causes an enlarged heart, which may result in chest pain, dizziness, and even a sudden cardiac arrest.

Here to talk to us about the molecular motors that power the heart, mutations that enhance function, and UVM research discoveries in this area is David Warshaw, PhD, Professor and Chair of Molecular Physiology & Biophysics at the University of Vermont.

What is enlarged heart?

Warshaw: An enlarged heart is a heart that’s larger than normal. The interesting thing is that the heart is one of our biggest muscles. So, just like weightlifters who exercise and see their muscles enlarge, your heart enlarges, too. Sometimes it enlarges for good reasons. Sometimes it enlarges for bad reasons, and we’re going to talk about why it enlarges for a bad reason.

What are the bad reasons?

Warshaw: Some of them are genetic mutations. There are probably 1 in 500 Vermonters who have genetic mutations to proteins called molecular motors that power your heart. They are literally motors that convert energy into power and make your heart pump blood throughout your body.

For some reason, these genetic mutations impact the structure of the heart, and the heart enlarges to a point where the chambers of the heart (which pump your blood) become so large that they can’t pump as much blood. Therefore, there’s a detrimental effect to the person who has the condition.

How does somebody live with enlarged heart?

Warshaw: Well, the problem is, in some cases, they don’t. You might be watching TV, and hear about a basketball player at the age of 22 who dies on the court, and then they do an autopsy and say: “Oh, he had an enlarged heart.” Nowadays, we can also understand that person’s genetics. Nine out of 10 times that person has one of these genetic mutations.

Who is at risk?

Warshaw: Anybody who has the genetic mutation, but the issue is, how do you find those people?

So this person who I just gave you an example of, who might have died suddenly during a sporting event, you can then go back and look at the family tree and see whether that person’s uncle, father, mother, or other family member has or had a heart condition, and potentially one at a very early age. If that family member is still alive, you could ask for a DNA sample and confirm whether they have the mutation.

Now, just because you have it, doesn’t mean you’re going to die suddenly, so I don’t want to scare people. You may present as someone with a typical cardiac problem, where you might feel dizziness or shortness of breath, or maybe even chest pain. And so, you will see a cardiologist, and then you could be treated.

The critical point here is, if somebody in the family presents at an early age, it’s not a bad thing to talk to your cardiologist. I always say knowledge is important. And if you have that data, you can make informed decisions.

You mentioned an athlete as an example. Is this something that is often seen in athletes?

Warshaw: It’s interesting. We all have the same odds. I would say 1 in 500 athletes could have it because that’s the percentages. What’s interesting is that some countries require children to have an electrocardiogram or EKG before participating in sports. In fact, if you have an EKG, you can predict if somebody has the disease. And so, the question is, “Should we be doing that for all our athletes?”

You studied Electrical Engineering when you were an undergrad student. Could you tell us about your journey from engineering to physiology and biophysics?

Warshaw: When I was a high school student, I was good in math and science. Back then, you went to your guidance counselor, and they said: “Well, you’re good in math. You should be an engineer.” So, that’s how I decided to be an engineer.

During the process of taking engineering courses, I came across courses in biology and courses in the human body and anatomy, and I realized that, in fact, the human body is probably one of the most beautiful engineering design systems in the world, and you can apply engineering principles to the body.

And I switched over, after getting my Bachelor in Electrical Engineering, into Physiology and Biophysics, and the rest is history.

Now you’re an expert in myosin molecular motors. Can you tell us what that is?

Warshaw: Myosin molecular motors are tiny proteins. Every muscle in your body is made out of protein. When you go to the store and buy some chicken breast or piece of meat, it’s made of protein, and the biggest component of that meat is called myosin.

Myosins are tiny, tiny molecular motors. They are one ten-thousandth the size of a human hair. Each one of those, and it’s trillion partners inside a muscle in your heart, generate force and motion. It’s these tiny motors that are necessary for your heart to pump blood.

What the heart does is it orchestrates all of these motors at the same time to generate force so your heart beats regularly, you know 70 times a minute. The interesting thing, speaking about engineering, is I did a quick calculation once, and the heart actually beats about three billion times in your lifetime. A car’s engine probably only has about a third of a billion revolutions to its life, so Mother Nature’s built a better engine.

How do myosin molecular motors connect to enlarged heart?

Warshaw: We can measure the forces of these tiny molecular motors. We know that the mutation that people present with is a single mutation to these proteins.

Now, proteins are made out of amino acids. Myosin is made out of 2,000 amino acids, and if we think of it like an engine of a car, it’s made out of 2,000 nuts and bolts. If you change one bolt, all of a sudden, the engine doesn’t work properly.

Mutations usually make things work poorer than better. But, when we measured the forces of these tiny, little molecular motors, they generated more force than normal. So, heart enlarges because it’s actually ripping itself apart internally. It’s overpowered. It’s like putting a Ferrari engine into a Volkswagen chassis. Going to the race course, it’s a recipe for disaster.

The interesting thing is, now, based upon this information, there are companies creating drugs that are trying to put governors on these tiny, little molecular motors so that the heart now beats with the proper amount of force and power, and it doesn’t injure itself internally.

How does this information extend to other domains of health?

Warshaw: What’s interesting is that myosin molecular motors have other functions, not just the ones that are associated with muscles. Think of the insulin granules and insulin being secreted. Insulin is packaged in tiny, little vesicles inside the cell, but they have to get from the center of the cell to the edge of the cell, so that it can be secreted. And, guess what? These tiny, molecular motors are attached to the vesicles, and they crawl and drag these vesicles right to the end of the cell. So, what I learned in the heart can apply potentially to diabetes, in terms of insulin secretion.

What other research is happening at your lab at UVM?

Warshaw: Myosin is one protein that’s found in the heart. There are some other proteins. One in particular is called myosin binding protein C. As the name sounds, it binds to myosin, and what it can do is it can change the way myosin generates power normally. And, so, that’s become a target. If you want to try to change myosin, this molecular motor’s power generation, and therefore how strong the heart beats, if you can target this other protein that binds myosin, then that’s another avenue of investigation, which my lab is at the forefront of doing right now.

Wow. All these interesting things happening at this very, very tiny level inside of you.

Warshaw: That’s why I enjoy coming to work every day. It’s a lot of fun. Mother Nature holds back enough to make me come to work the next day.

Where else do you see the future of research, and specifically in terms of enlarged heart?

Warshaw: There are a lot of efforts to do a better job in cataloging people who have it. Rather than waiting for it to happen, why not be proactive? So, I predict within years, and not too many, that every child who is born, a blood sample will be taken, and their entire genome will be done, meaning all the genes in their body and, therefore, you’ll be able to predict in advance who has it.

Now there’s the ethical questions associated with that. But, personalized medicine is the future. Everybody will know what the gene make-ups are and, given the information we now know about how genes relate to certain diseases, everybody will have their profile in their pocket, and then they can present and say: “Well, I have this gene that does such and such,” and they’ll tailor medicine towards the individual.

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