Engineering Cardiovascular Health with Jessica Wagenseil

YouTube video

In this episode of Engineering the Future, Jessica Wagenseil, professor of mechanical engineering & materials science and Vice Dean for Faculty Advancement, discusses how her interdisciplinary work combines mechanics and biology to understand cardiovascular health. Wagenseil uses computational models to predict disease progression and collaborates with physicians to help inform clinical decision-making and future therapies. She also shares her experiences with teaching, mentorship and outreach, including her work with the BrightPath STEAM Academy to encourage local youth interest in science and engineering.

Jessica Wagenseil: There's kind of a theme in the literature that we're only as old as our arteries. And so yes, there is wear and tear over time. There is aging induced changes in the mechanics, but in the diseases we study, there's actually genetic mutations that make it so that the wall is not made properly and that accelerates some of those changes. 

Shawn Ballard: Hello, and welcome to Engineering the Future, a show from the McKelvey School of Engineering at WashU. Our theme this season is Engineering Human Health. I'm Shawn Ballard, science writer, engineering enthusiast and part-time podcast host. Today I am here with Jessica Wagenseil, who is a professor in the Department of Mechanical Engineering & Materials Science, as well as the Vice Dean for Faculty Advancement. Welcome, Jessica! 

JW: Thank you so much for having me.

SB: I want to start first with a broad view of what you do, which is biomechanics and mechanobiology. Are those two terms different in any meaningful way, and what do they actually mean?

JW: Yeah, thank you. So they're not just a rearrangement of the letters, but biomechanics is the study of mechanical behavior and properties of biological systems. And so an example would be determining the mechanical properties of arteries, so that you can predict wall stresses and then predict when it might fail. And then mechanobiology is the study of the effect of the mechanical environment on the biological systems. And so an example there would be the cell's response within the artery to those wall stresses so that they might make more proteins in response to those stresses. 

SB: Okay, so it's kind of a structure and then function, is those two parts that come in. Cool. So how does the study of mechanics actually impact human health? I found myself wondering how much like a machine actually is a human body?

JW: Yeah. So for the first part of the question, if we go back to those two parts, biomechanics and mechanobiology. So for biomechanics, we need to know, for example, if you have a disease such as an aneurysm, which we study, right, we need to know what the strength of the wall is and the properties are so that we might be able to predict when we should intervene. And then for the mechanobiology, right, in a disease like hypertension, which we also study, the cells respond to those increased stresses and actually change the proteins in the wall and can make the disease worse.

And so we are a machine, but we're a machine that can grow and respond to the mechanical forces on us, unlike a typical machine.

SB: Okay. So getting into that sort of the machine parts of the human body you've mentioned, you know, arteries and how those things grow and expand. Can you sort of tell me a little bit more about that? So I'm sort of aware there are arteries inside. They carry blood around. Tell me more about the vascular system. What exactly does that entail from a sort of human body standpoint? 

JW: Yeah. Right. So your arteries are the vessels that carry blood away from your heart to all the rest of your body. Right. So to get blood to our fingers and toes, we need arteries to deliver that blood. And the one that we study in particular is the aorta, which is the largest artery off of your heart. So all of your cardiac output comes out your aorta, and then it goes off into branches into all the different parts of your heart. And the aorta needs very specific mechanical properties to do its role and to deliver that blood. 

SB: Okay. So I'm just sort of getting a sense of when you talk about the aorta as the largest artery, what size is that? So I have a sense that like my heart is kind of the same size as a fist. Is that right? So how big is the aorta and how big can it get as it stretches?

JW: Yeah. So your aorta is about an inch in diameter or two and a half centimeters. And it stretches about 20% every time your heart pumps blood. And when it stretches, it actually stores something that we call strain energy. So if you pull on a rubber band, it's storing energy when you pull it, and then you let go, it snaps back. Right? So that's exactly what your aorta is doing. So your heart pumps blood out, it stretches, it stores that energy, and then it actually kind of snaps back and pushes blood downstream and helps get it to the rest of your extremities. 

In some of the diseases we study, when your aorta gets to about four centimeters, it might be time for a surgical replacement.

SB: Okay. Because I was going to say, just as you described that, you know, as we're sitting here talking, right, your heart's pumping, every single time your aorta is doing that, that stretching and contracting, snapping back like a rubber band. And from interacting with rubber bands, I know there's only so many times that you can do that. Is that part of what leads to that? That sort of just wear and tear that happens over time is the normal functioning of your, you know, the elastic part of your arteries?

JW: Yeah. So is that certainly a little bit of it, right? So there's kind of a, there's a theme in the literature that like we're only as old as our arteries. And so yes, there is wear and tear over time, there is aging induced changes in the mechanics. But in the diseases we study, there's actually genetic mutations that make it so that the wall is not made properly, and that accelerate some of those changes.

SB: Okay. All right. So let's kind of dig more into that. You know, you mentioned some of these various things that can go on with arteries. What drew you into studying the sort of cardiovascular machine that is at work there? What were some of those maybe particular diseases or those big health questions? Is that what drew you in, or was it something else? 

JW: Yeah. So it actually started in undergrad. So I went to UC San Diego and I studied bioengineering. And at that time, the curriculum there was heavy in biomechanics. And so just learning all about biomechanics of all kinds of different tissues and parts of your body. And this idea that, you know, we were or are mechanical machines, but they can grow and remodel was really interesting to me. And then I did undergraduate research in a lab that studied cardiac mechanics, the mechanics of the heart, and just became interested overall in the cardiovascular system and this concept of biomechanical remodeling and mechanobiology. Because cardiovascular disease is still the number one global killer.

SB: Okay. Yeah. And what does that mean, sort of numbers wise? It's the number one global killer. I know it's a big problem, right? We all need our hearts to be pumping. And now I'm every time I'm thinking like, oh my gosh, it's stretching and relaxing. And how much closer am I to, you know, it being sort of stretched for the last time? That's very scary.

JW: Yeah. I mean, so in our normal lifespan, right? So there, there is an increased risk of cardiovascular disease with aging. But in our normal lifespan, it is meant to stretch and relax, you know, all of the times over our lifespan. So actually, the protein that we're really interested in is called elastin. And it has about a 50-year half-life. So it actually doesn't start degrading until you’re about my age. And then, but it's made to last for the human lifetime.

SB: Okay, it's made to last for the human lifetime. But you mentioned, you know, there are other factors at play, right? Sort of, I could imagine, you know, genetics or other diseases. Tell me more about those particulars that get into, you know, perhaps reducing that span of the elastin that we that we need to keep our arteries, our aorta going as it's supposed to.

JW: Yeah. So we're interested in genetic diseases that affect the elastic fibers. And so if you have a mutation in some of the proteins that are involved in elastic fiber assembly, you can have either aneurysms, right? So there's several proteins that lead specifically to aneurysms or this dilation of the aorta, so bigger than your two and a half centimeters. You can also have a mutation in elastin itself. And that actually causes the stenosis or closing off of the aorta. So it's smaller than it's two and a half centimeters. So you don't want either one, right? You don't want to dig too big or too small.

SB: A real goldilocks situation there.

JW: Yes, exactly. And so we study these genetic mutations so that we can understand, you know, how the mechanics change, how the disease progresses, and how we might be able to treat it and predict it so that we know, you know, when to intervene in a human or also to test some therapeutics.

SB: Can you tell me more about the sort of maybe facilities, collaborators, like of course, a lot of our faculty work closely with, you know, folks on the med campus? What does that look like for you for your work? 

JW: The main collaboration I have with the medical campus is Dr. Braverman who runs an aortopathy clinic, right? So he sees patients with genetic mutations that lead to these diseases that we study. And so that's been a really great collaboration because we can get his insight into what, you know, is actually his patients are going through and what he sees in the clinic. And then we're working with him. We have access to some of the human imaging data that's been deidentified, but we can now see the geometry of these diseases. And then we're using those imaging data for computational models to understand the wall stresses and then also how the disease might progress in response to those wall stresses.

SB: Okay. So lots of various, you know, I guess interdisciplinary work; you mentioned imaging, modeling. Can you dig in a little bit more for me in terms of, you know, what that looks like maybe kind of a typical day of research, you know, whether that's in the lab or, you know, I could imagine a lot of like computer work with that kind of modeling. What's a typical day like for you?

JW: Yeah. So it's actually probably better to ask what a typical day like is for my students or my postdoctoral fellows, because I'm not the one in the lab actually doing experiments anymore or running the models. And so, you know, I help conceptualize these ideas and then start the collaborations and then work with the students to get the projects done. But my students are the ones who are actually doing experiments. So whether it's on mouse aorta or on other aortic tissue that we may get from collaborators to understand mechanical behavior, or if it's in cell culture where they're, you know, trying to understand how the cells are responding to these mechanical signals, or if they're sitting at the computer running computer models.

And then my day is, you know, I meet with a lot of them to kind of go through their results and think about what they mean or troubleshoot problems. I also teach. I also have this vice dean role. And so I work on things like tenure and promotion for faculty. And so from my point of view, it's really varied, which is nice because I can kind of pick and choose, you know, what I feel like working on that day. 

SB: Amazing. Okay. So you mentioned, you know, obviously, mentoring your students, doing teaching as well as your other, you know, service in the school. I also know that you do quite a bit of outreach here, you know, through McKelvey, but really focused on local students here in St. Louis. Can you tell me about sort of the major programs you're involved with and what you get up to, you know, sort of outside the classroom and outside the lab?

JW: Yeah. So we work with the BrightPath STEAM Academy. And it was started by a WashU alum, Marcia Brown-Rayford. We've been working with them for about five years. And the focus is on exposing local St. Louis youth to STEAM, right? So science, technology, engineering, art and math. And then we run a one-day summer program where the kids come to the WashU campus, and they have different topics that they can choose from to learn. And then they do lab tours to understand like what's happening at the engineering school. And then we also run a six-week fall program on Saturday mornings, where we have six different engineering professors that do a one and a half hour hands-on activity related to their research to introduce them to those topics.

And so it's great because the students are always super excited when they come to campus. And then most of them then tell me like, “Well, I'm going to go study this engineering,” or “I'm going to go study, you know, this.” And we always have a fight because Marcia is a ChemE alum and I'm mechanical engineering. And so we always ask the students, you know, which one they prefer. But as long as they're interested in something engineering, then we think of that as a win.

SB: Yeah. What are some examples of those kinds of, you know, those programs you mentioned, you know, the labs they get to go into? What are some of the ones that really capture the kids’ interest? Can you sort of paint me a picture of that?

JW: Yeah, yeah. Yeah. So we just finished the six-week fall program. So one of the examples was Marcus Foston, who's in energy, environmental & chemical engineering. So he's trying to work on making materials from biologics to replace plastics. And so he had the kids, they make basically like bouncy balls, but out of biological materials. And so they can combine the different materials in different ways. And the goal was to figure out what components they could use to make the ball bounce the highest.

SB: Oh, I love that.

JW: And so they got to mix things, play with the balls, and then kind of try to optimize their recipe to for, you know, a design criteria, which was the highest bounce.

SB: Okay. I can imagine that being a lot of fun to do the testing component. What about outreach, and, you know, maybe here in St. Louis in particular, really, you know, made you say like, this is something that's worth, you know, more of my time than I'm already, you know, devoting to research and teaching and all the many things that go into being a professor? 

JW: Yeah. Well, so one is on just the outreach in general and the pipeline, right? I mean, so we all know that as we go up in the engineering pipeline, we lose diversity, right? So we lose women, we lose underrepresented groups. And so part of this is trying to address the pipeline, where if we can try to get kids interested in an earlier part of their education, and especially kids who may not see it otherwise, right, can we keep them interested in engineering? And so that we end up with an engineering profession that looks more like, you know, the U.S. overall population.

The other part, you know, the St. Louis part, right, you know, WashU is a part of St. Louis. We're not just this isolated campus. And so interacting with the community, I think, is really important. So they learn a little more about WashU and the, you know, kind of what we do here, and that then, you know, have this more tighter connection with the community. I’d say those are, you know, two of the main reasons.

SB: So you're doing all this research in your lab with cardiovascular, you're doing this outreach. And then I know you're also affiliated, on top of all that, with the Center for Women's Health Engineering. What kind of projects are you working on in that arena? 

JW: Yeah. So most of what we do in that area is on sex differences. And so, you know, for example, in this model of aneurysms, we found some really interesting differences between males and females. And so, you know, in the past, there wasn't a big focus on always using both sexes in all of your models. But the NIH, National Institutes of Health, has made a big push in that direction. And what's great is that now there's all these interesting things coming out about, in our hands, like the female mice, they have a much slower disease progression, and they have much better outcomes than the male mice. And we don't understand why.

SB: Interesting! 

JW: Yeah. And so now we can kind of dig into, like, is it sex hormones? Because there's some hints that maybe estrogen plays a role, or is it sex chromosomes? And so that's kind of the side of things that we do associated with women's health. 

SB: Interesting. Okay. So I know it's just in mice, and, you know, I don't want to extrapolate too far. But is that, you know, so far, does it seem like that is a similar thing going on in humans?

JW: Yeah, for sure. And so, yeah, a lot of people haven't looked at cardiovascular health separately in men and women. But it is very important to do so, especially because so for outcomes, like for aneurysms, if they're using the same criteria for men and women, those may not apply. Like, I told you, they actually go by size right now on when to intervene. But women have smaller aortas in general, because we're smaller overall. And so it's very important to kind of think about those differences in men and women.

And then also, women tend to have better cardiovascular health when they're younger. But then the changes accelerate as we get older, maybe due to the changes associated with menopause and things like that. But we need to study them separately in order to understand these things.

SB: Right. Okay. Do you think, and this is perhaps branching a little out of your expertise, but I feel like that's sort of a recurring thing that comes up when we talk about, you know, really even common health conditions that people face, is that they've been extensively studied in, you know, men, predominantly white men. And what researchers are finding, and it sounds like you're finding, is that that's just not actually representative. Can you say more about that? Like, it sounds like, you know, you have this sort of small sample with the mice and, you know, women's hearts. Do you think that's part of a broader push that's going on?

JW: Yeah, for sure. I mean, so studies that were done in white male are representative of the effects and outcomes in white males. Right. And so extrapolating those to anything else is suspect. And so I'm really happy that there is a push to, you know, diversifying the group that we're studying, and actually looking at them by group and not trying to extrapolate from one group to another.

SB: Okay. And it sounds like you're already seeing, you know, how big that difference can be. What impacts or interventions have you already been able to sort of see go into either clinical use or recommendations for patient care, that kind of thing?

JW: Yeah. So most of what we study is what I would call, you know, basic fundamentals. And so, you know, using animal models, using cell culture, using some, you know, in vitro studies. But more recently, we actually have two things that are a little more translational.

One is we're actually testing a therapeutic that might prevent some of this elastin degradation that you see in disease and over time. And so we're testing that right now in the mice. And so that's exciting that it might actually, you know, be something that would be used in the clinic at some point.

And then the other one is this collaboration with Dr. Braverman, where we now have access to human images. And so, you know, we've done a bunch of computational modeling in the mouse aorta. But now we can do some of that in the human aorta. And again, try to, we're trying to pull out mechanical biomarkers that might be able to be used by surgeons in addition to size. Because we know that size alone is not enough. And what we really care about is strength, right? Like when is the wall going to fail? And so by this modeling, we can pull out some of those parameters and try to understand, you know, if this additional information might help surgeons make a better decision.

SB: What is the advantage? What do you see as the advantage of having, you know, a mechanical engineer, you know, rather than someone who's, you know, maybe a biologist or a biomedical engineer teaming up with physicians in this way?

JW: Yeah. And so the biggest part for us is this mechanics, right? I mean, so I've come back to that a few times. But your aorta is a pressurized cylindrical vessel with flow through it. And so we know that all of those things are associated with mechanical stresses. And so you can look at cells and cell signaling. But you, in my opinion, you can't separate that from the mechanical environment. And so as a mechanical engineer, we can bring in the understanding of that and the appreciation of that, and then ways to model that or ways to investigate that further. That is just a really important component of understanding what's happening in the body.

SB: So you've talked about a few of these, you know, projects that you've got going on. Is there one that you've got coming up that you're particularly excited that you could share with us?

JW: Yeah. So I talked about these two translational ones. Those are exciting to us. Another one that's relatively new is focused more on the mechanobiology. So most of our previous work in the past has been, you know, more on the biomechanics side. And a lot of it's because the mechanobiology is hard. We don't fully understand, you know, what are these things that are sensing these changes in the mechanical environment. But there's been a lot of work lately on what people call mechanosensors, right? So proteins in the cell that can sense changes in the mechanics.

And so we have a new project right now where some of these mechanical biosensors have been may play a role in the stenosis disease that we see. So in stenosis, it's a mutation in elastin. And so by reducing the elastin, we think we've really changed the mechanical environment around the cell. And there may be a mechanosensor in the cell membrane that's actually sensing that change and then responding. So we have a new project to look at that and kind of dive deeper into that side of things.

SB: Okay. And would that be sort of looking at the, you know, the structure of the cell wall or the genetics or both?

JW: Yeah. So what we're doing in terms of genetics, right? So we're basically looking at gene expression changes, but we're looking at gene expression changes in response to like mechanical stretching of individual cells, both within a normal wall and then within one of these walls that have less elastin. And trying to understand how the actual environment around the cell changes the stretch of the cell and then expression of this mechanosensor that then may lead to downstream changes that cause stenosis. 

SB: Okay. I'm again running up against this. Like, I don't always think of the environment as having a sort of a gene component, right, or a gene impact. But that is what you're seeing. These things are sort of all tangled up. And, you know, if they start off smaller, right, there's some sort of fundamental gene expression, and then the way that they actually operate, you know, sort of in turn impacts that. Is that right?

JW: Yeah. So that's kind of bringing back, so this project, you know, leans heavily on the biology, but again, still has the mechanical engineering component of that everything is dependent on like stretch or stresses in the cell. 

SB: Okay. So the actual like sort of physics, like the mechanics of the system, then changes the biology.

JW: Yes. Yes. 

SB: Mind blown. Okay. I love that. That is again great news for those of us, people like me, who thought like, I don't want to study biology. I want to study physics. But, you know, then what impact am I making with that? And human health is such a big one. Do your students talk about that with you? Is that sort of a motivator for them? You mentioned how you got into this. What about your students? What do they tell you?

JW: Yeah. So I think the human health part is a huge component. So many of them, like you were kind of saying, like to make a difference, right? So we like to see, you know, some sort of, you know, societal or broader impact of our work. And so, if you can say that the things that we're learning will help human health or maybe, you know, come up with a treatment for cardiovascular disease or even just guidelines for, you know, when to intervene, I think that makes a big difference.

And then we're about half biomedical engineers and half mechanical engineers in the lab in terms of my students and postdocs. And so that's also nice to see the combo of the two. And then, you know, push a little more biology on the mechanical engineers and a little more mechanical engineering on the biomedical engineers. 

SB: Okay. Yeah. Good to broaden their worldviews in that way. I guess related to that, I always love to close these conversations by asking for a media recommendation. I'm always looking to, you know, to read something, see something new. And so, for you today, I'm specifically interested if you have a recommendation for me of mechanical engineering out in, you know, popular books, TV, movies. Something where you've maybe been able to see yourself and thought like, oh, that's really it. Or maybe conversely, that's really not it.

JW: Yeah. Yeah. So it's hard to come up with specific mechanical engineering examples. So I will tell you one book I really enjoyed in the past few years was called Project Hail Mary. So it's about an astronaut who wakes up and he's the only one left alive in his ship. And he has to figure out, like, you know, how to run the ship. And then, of course, how to solve the science fiction problem that is part of the story. But there's all kinds of good, you know, troubleshooting of all of the problems that happen. And so I identify with it because part of engineering is, you know, troubleshooting and coming up with a solution. And so he's doing that in, like, every chapter. So I really appreciated that in that book.

And I have one more, which is Lessons in Chemistry, which is not mechanical engineering, but is a story about a woman chemist and all of the biases and obstacles that she ran into. And it's just a really good story of resilience. And also, you know, lessons that hopefully we've learned a little better these days and how to treat both men and women in the sciences.

SB: Well, thank you so much for those. I have enjoyed Lessons in Chemistry, but not yet Project Hail Mary. So I'll be sure and check that out. 

JW: Okay. Sounds good.

SB: Well, thanks so much for coming on the show today, Jessica. This was a delight. I had my mind blown many times, and I look forward to chatting with you about what comes next.

JW: All right. Thank you for having me.

Click on the topics below for more stories in those areas

• Outreach
• Women & Engineering
• Podcast: Engineering human health (2025)
• Mechanical Engineering & Materials Science

Back to News