Anthony Rosenzweig, MD: Exercise-Induced Heart Growth

On Monday, November 12, 2018, the US Department of Health and Human Services will announce the updates to the 2008 Physical Activity Guidelines for Americans.

In addition to the guidelines, new research is being conducted to determine how exercise can protect the heart and its potential role in cardiac regeneration.

MD Magazine® sat down with Anthony Rosenzweig, MD, Chief of Cardiology at Massachusetts General Hospital and Co-Director of Corrigan Minehan Heart Center, at the American Heart Association Scientific Session 2018 in Chicago, Illinois.

Dr. Rosenzweig will present a session titled “High Throughput Profiling Techniques to Identify Pathways Unique to Exercise-Induced Growth and Protection,” on Sunday, November 11, 2018 at the meeting.

Interview transcript: (modified slightly for readability)

MD Magazine®: Can you discuss your presentation on exercise-induced heart growth and protection?

Rosenzweig: A few years ago, we got interested in studying exercise a model for the healthy heart. We had this epiphany that we know a lot more about what goes wrong in disease than what actually keeps the heart healthy. So, we wondered if we could use an exercised heart as a model to help understand what pathways protect the heart. To do that we’ve used a range of different high throughput profiling approaches to categorize every gene and molecule that changes in the exercised heart.

The three takeaway messages from that that we learned are, first of all, when the heart grows in response to exercise its fundamentally different from when it grows in response to high blood pressure, heart attack, or something else. From a really early stage the hearts look similar, but the pathways are very different.

The second is that exercise drives a process of birth of new heart muscle cells which is very hard to do in an adult heart. Adult hearts have a very limited capacity to repair or regenerate, and exercise is so far the only physiologic modifier that enhances that. So at least in animal models, it increases about five-fold if you exercise animals compared to not.

The final thing is that every pathway that we, or other people, looked at, that we see that’s functionally important in the heart’s response to exercise, also prevents against disease. So that means it is potentially a fertile area to identify new pathways that might be targets for drugs or medicines that might treat or prevent heart disease.

MD Magazine®: What are some current areas of research that are being explored in relation to cardiology and exercise?

Rosenzweig: I think one of the things that we’re particularly intrigued by is this idea that exercise enhances the low level of regenerative activity in the heart, meaning exercise enhances the ability of the heart to grow new heart muscle cells and potentially repair itself after an injury. So, if we could understand the pathways involved with that then maybe we could use those to repair a heart after a heart attack or in response to heart failure for example.

So, one of the things that we’ve done is tried to identify what are those cells that are dividing. What’s different about them? What are the particular molecular mechanisms that are involved and how can we exploit those mechanisms to try to enhance the ability of the heart? And we can do that genetically in animal models. So far, we don’t have a pathway that we have a medicine or drug that tweaks, but that’s ultimately the goal.

And then, one of the things that it’s intriguing about that is the heart is not the only organ that responds that way, the brain responds similarly, so exercise seems to be one of the few things that will drive birth of new neurons in the hippocampus, part of the brain that we didn’t think had the capacity to grow new neurons. So, we’ve wondered if are there, in fact, circulating factors that coordinate this. Are these just two different organs that both have the same response?

It’s easy to understand why the heart is involved in exercise, it beats faster, more vigorously in response to exercise. I’m a cardiologist but it’s harder for me to understand why the brain would respond or be integrally involved in the exercise. So, raising the possibility there may be circulating factors that drive the regenerative response, so started looking for those. There are now ways that you can take blood from humans or animal models and catalog all of the molecules that change in response to exercise and try to figure out if any of them, in fact, are driving that process.

I guess the other thing I would mention is we are very interested in which of these pathways would be druggable, and there are some of the pathways that are related to exercise that are already targets of medicines that are in early clinical trials for other indications, not for heart disease. So, we’re trying to see whether we can use those. In animal models they actually work remarkably well in restoring function to failing hearts, so now we’re trying to talk to the companies that are involved in making those medicines to see if they would be interested in pushing that further to see if it has potential to help people.