A Closer Look at Statins With Dr. Nazish Sayed

In this episode, we interview Dr. Nazish Sayed, an assistant professor in the Division of Vascular Surgery and the Cardiovascular Institute at Stanford University. Dr. Sayed has a unique role as a research faculty in the Department of Surgery and his expertise in vascular disease. We talk about the beneficial effects of statins on vascular function and how statins can prevent cardiovascular diseases. Dr. Sayed et al published a paper in Nature Cardiovascular Research in May 2023 on statins at the molecular level, and we discuss the challenges faced in getting the paper published (four years!). The episode concludes with a discussion of Dr. Joseph Wu, Dr. Joseph Woo, and Dr. Sayed's future research plans.


Transcript

Rachel Baker: [00:00:00] Welcome to ScrubCast Where we take a closer look at the research happening in Stanford University's Department of Surgery. I'm your host, Rachel Baker. Today, we're speaking with Dr. Nazish Syed. Welcome to the show.

Dr. Nazish Sayed: Thanks, Rachel. It's a pleasure to be here.

Rachel Baker: Dr. Syed is an assistant professor in the Division of Vascular Surgery and the Cardiovascular Institute.

You are unique in this department in that you are purely research faculty. How did you end up with all the science without the slicing into humans?

Dr. Nazish Sayed: That's a, that's a really good question that what is a non-surgeon doing in the division? In the

Rachel Baker: Department of Surgery.

Dr. Nazish Sayed: That's correct. Um, I feel actually it is the right match and the marriage between research and clinical.

Because I think that is where my translational experience can bring along. It is very important to understand, uh, the bench side to go to the bedside [00:01:00] and, you know, I bring in that research experience, which we can hopefully tell the surgeons what needs to be done or what doesn't need to be done by knowing their cells in a dish, you know, by knowing what is happening molecularly.

So that, uh, you know, our amazing surgeons can actually improve surgical outcomes.

Rachel Baker: Definitely. That's awesome. How did you end up at Stanford? I mean, you just, you kind of went through the little bit of, like, you were gonna get your MD, then you decided to get your PhD.

Dr. Nazish Sayed: Yeah. So, I did my MD, and I did my, uh, in cardiology.

I loved it. Well, there's something missing, you know, I was like, you know, as soon as I finished my clinical academic, I was like, this is not the only thing I want to do. I want to be a little more creative and understanding this heart disease dysfunction. So I said, the best way to do it would be to do a PhD, not an MD [00:02:00] PhD, but a PhD separately, where I can learned from many different experts of how many different tools are applied to understand heart disease.

And that's what I did. I did my PhD. Then I decided, okay, well, I want to now switch gears and try to look into vascular disease and not just the heart dysfunction. So that led me to go into the vascular. And the next, you know, I ended up in the division of vascular surgery among surgeons, which I think is amazing.

I learned a lot from all the surgeons. And I hope I can contribute to them about, you know, understanding at a molecular level. So this is, this has been the journey going from clinic to a non clinic, from a heart to the vasculature.

Rachel Baker: Well, so I brought you on the show today to talk about statins. I was having a joking conversation with my GI about what five medications every person should be taking, and statins was one of them.

And then I related this story to my sister-in-law, who's an internal medicine doc, uh, [00:03:00] over the holidays. And her list also started with statin. So I had I started having a real case of FOMO here because I'm not on a statin and I'm not really sure what it is. Can you help explain?

Dr. Nazish Sayed: Sure. You know, rightly said, it is a common drug which has amazing effects and people should be on it.

I can tell you I am on a statin and it's not because I've been doing research on statins because it is a really wonderful drug. It has many pleiotropic effects. Initially, we thought statins was only to lower the bad cholesterol, which was the LDL, which it does. You know, it takes out the cholesterol from the plaque and it is able to decrease the risk of coronary heart disease.

But I'll tell you, as more technology and tools have been brought about in the research landscape, We're able [00:04:00] to now dig into what other effects or, uh, you know, pleiotropic effects of statins could be. And this is where I feel, uh, the beneficial effects of statins kick in. You know, we thought about cholesterol, but it's actually important for improving, uh, vascular function.

It is, has anti-inflammatory effects, you know, uh, people have started to now recommend it for cancer patients because it can reduce inflammation. Uh, which we could be brought about by the vasculature. I mean, you know, you think about the VAs and then specifically statins effects on the vasculature is, is crucial.

Now what I'm gonna say, Rachel, is that your vasculature is like the plumbing in your body. It starts from the brain all the way the, to the top, from the top to the toe. Uh mm-Hmm, . Any blockage in this plumbing could have many effects, and statins specifically is helping. Clock, I would say it didn't in layman took the [00:05:00] vasculature.

So that is why statins was recommended by a GI as one of the five, you know, common drugs.

Rachel Baker: It's the Dr`ano of my vasculature.

Dr. Nazish Sayed: There you go. You put it right. It is .

Rachel Baker: Well, you did some research looking at how statins work on the molecular level. I found a paper published in Nature Cardiovascular Research from May 2023, but I must admit, I thought YAP was a sound that my dog made.

So, can you maybe put this into terms the average patient could understand?

Dr. Nazish Sayed: Right. No, no. So thanks for, thanks for reading the paper. So. You know, that's where we started looking into the unknown effects of statins at the molecular level. So, of course, it's going to lower the cholesterol. But we found that, you know, statins have a very beneficial effect on the endothelial cell.

So this is a cell which is lining your [00:06:00] inner wall of the vessel. It is an amazing cell, which is basically a monolayer. And this statins has an effect on That one specific cell type, you know, but as we age, as we are going through the elements of our life, we have a lot of inflammation. We have a lot of, uh, you know, buildup of plaque and buildup of our endothelial cells starts to change its phenotype from a regular functional endothelial cell, something which is called as an endo MT, which is going from an endothelial to a mesenchymal.

And clearly that mesenchymal stromal cells are not good for you. So what we found from this paper was that statins, in addition to lowering all the cholesterol, has an effect on the chromatin. So this is your tightly bound DNA within the nucleus, which in a regular inflammatory or other condition kind of slightly opens [00:07:00] up and pushes that cell to become a non-functional cell.

Statins basically are Preventing that pathological trans differentiation from a functional endothelial cells to a non-functional endothelial cells. And this is, this is, uh, you know, really good because it can prevent from an early stage. Let's say if we identify someone who is borderline atherosclerosis or borderline heart dysfunction, if they start on statin, our assumption is that maybe we can prevent that.

Sort of semi-permanent change in the DNA, the chromatin, which will push it to become a non-functional cell. So that's, that's where the story comes in of this effects of statin.

Rachel Baker: That's super cool. I love it. Well, so I eat right. I exercise. My cholesterol is golden. Um, should I be asking my GP to put me on a prophylactic dose of simvastatin?

Dr. Nazish Sayed: Rachel, that's an excellent [00:08:00] question because, you know, do, does everybody needs, uh, statin? I mean, you know, definitely there's beneficial effects, but I think we do need to be a little bit more cautious of just not, you know, over prescribing a drug when, you know, it's not warranted. Yeah, I. I definitely think statins are good for people who have, of course, you know, high cholesterol or people have predisposing conditions or comorbidities like diabetes or a borderline hypertension.

Now, those patients who doesn't, who, who do not have fulminant heart dysfunction or vascular dysfunction, I think those could be taking the beneficial effects of the statins I think. So, I mean, you mentioned you eat healthy, you exercise. I, I don't think you would need to take a statin, you know, but, you know, we have our yearly physical done and if we detect anything, I think it is a really good drug to go on to, you know, early prevention can [00:09:00] prevent a lot of downstream negative effects or consequences.

So you don't need it, but there are many, many people who can benefit from being on it.

Rachel Baker: Well, so we're not putting it in the water just yet.

Dr. Nazish Sayed: Not yet. You know, there's much more discovery to be done of these effects of statin. Not just in cardiovascular. I think there's beneficial effects in, uh, people who suffer from cancer.

Rachel Baker: That would be a really interesting, That'll be my follow up podcast episode with you. Well, so before we leave the topic of research behind, I wanted to talk to you about your paper in nature. I think. We all know that the road to publication isn't paved with cheese. What challenges did you face while trying to get this paper into a journal and how did you overcome them?

Dr. Nazish Sayed: Yeah, getting into, you know, into a high impact, good journal is always a struggle. And, you know, you're trying to convince not just those three [00:10:00] reviewers or four reviewers who are the other side, but also You know, we strive to make sure that the readers really enjoy reading it and gain something and take it to their own lab.

So, you know, with my mentor, Dr. Joe Wu, who was a co senior author with me and the first author, Chun, uh, it did take a long time to get to this publication. So, you know, it was a struggle. It took us about three to four years to get this paper out. Uh, almost about a year to do the revisions because we were trying to show The beneficial effects of statins.

Other than the cholesterol lowering effects, uh, which, which is so, you know, we had to go leaps and bounds to kind of prove our hypothesis. And you can see it in the paper. We have almost about seven or eight figures trying to prove it. With many different ways. Um, and, uh, you know, the, the key was to tell the readers and the academic.

People that, you know, [00:11:00] satins are like an old drug with new tricks. And when you are trying to say that it's an old drug with new tricks, I think we need to prove above and beyond, which we did in the publication. So yes, there were some roadblocks of trying to prove, you know, any good journal. It takes longer time.

But, you know, I'm glad it's out there, uh, for people to read it.

Rachel Baker: Well, so I always ask. My, uh, guests, the same two questions. Right. And the first one is, Who is a surgeon you admire and why? This might be a weird question for you though, not being a slicer and dicer.

Dr. Nazish Sayed: So, uh, not really. You know, being in the vascular surgery or even in cardiology, I did my, you know, clinical cardiology, but then I decided not to MD to my PhD separately into vascular biology, but we work with surgeons all the time.

You know, one of the surgeons, which I've always looked up since I came at, you know, became a [00:12:00] faculty here and even as a postdoc before was Dr. Joseph Woo, the other CT surgeon, Dr. Woo. And the reason is because not only he's doing absolutely phenomenal work of giving people a new heart, but he's also taking the work in his lab and trying to discover other ways of improving heart function, uh, but not forgetting that we still need a new heart.

I mean, there is no way around it, but is there any other ways we can do it? Prevent the heart transplant to occur. But if we do have to do it, what are the good ways we can extend that thing from happening? Dr. W. O. O. is one of them I look up to because I think he has done phenomenally both at the clinical as well as the lab side.

Awesome.

Rachel Baker: Um, this one should be cross functional. What is the best advice you have received in 10 words or less?

Dr. Nazish Sayed: okay, 10 words. I mean, I got a lot of advice. [00:13:00] Yeah, but, uh, I'm going to count the words afterwards, Rachel. So let me say this. So my mentor, Dr. Joe Wu, so W-U, who's the director of the Cardiovascular Institute.

Um, whenever I, you know, as a, as a postdoc in his lab, his advice, I have tied a knot to my shirt. You know, on. It's a not. So I try to remember it every time is you try to keep your head down and continue working and hard work always pays. I hope that's 10 words. I mean, let me let the listeners count the words but that's the advice I always keep in mind that hard work always pays you keep continuing to do on.

So, what you're really passionate about.

Rachel Baker: Well, that brings us just about to time, but I wanted to ask you one last question, and that is, what's next?

Dr. Nazish Sayed: So I think, um, you know, many things. [00:14:00] One, of course, we want to dig deeper with the statin study, because, you know, we really want to understand the other effects, beneficial effects of statin.

What are the, um, Molecular molecules, which might be involved in the crosstalk with this thing. So we want to dig deeper, do some mouse studies. But I think in general, I think the next thing is, um, try to bring the importance of the vasculature, uh, in the realm of cardiac dysfunction. I mean, I think as a cardiologist, we all are quite myopic when we think about cardiology and think only about the beating heart cells.

But I think. If we dig into the vasculature and try to understand that if we can improve the plumbing, there is a very good chance we can improve the, uh, kitchen sink, prevent the kitchen sink from leaking. So I think that's what I really want to strive in my lab is to try to improve the vasculature, try to understand a vascular disease.

Which will help us improve [00:15:00] heart dysfunction and improve brain dysfunction. Because, you know, there's a very rich blood supply in the brain. So, that's what we're kind of pushing the boundaries and trying to study the effects of the vasculature on other organs.

Rachel Baker: Fantastic. Thank you so much for coming on the show today.

It was a pleasure talking to you.

Dr. Nazish Sayed: Absolutely. The pleasure was all mine.

Rachel Baker: And that brings us to the end of another episode. If you like Scrubcast, we hope you'll tell your friends and subscribe wherever you get your podcasts. Scrubcast is a production of Stanford University's Department of Surgery. Today's episode was produced by Rachel Baker.

The music is by Midnight Rounds. And our chair is Dr. Mary Hawn.

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