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Gene 'Switch' Mimics Exercise

Genetic Trigger May Help Heart to Repair Itself

Everyone knows that exercise is good for you, but scientists have understood surprisingly little about how physical activity affects the heart itself. Now a recent study by scientific team of collaborators from BIDMC and the Dana-Farber Cancer Institute provides enlightening insights into the genetics of exercise - and provides yet another reason for everyone to keep moving!

Dr. Anthony RosenzweigBIDMC Director of Cardiovascular Research Anthony Rosenzweig, MD, together with DFCI scientist Bruce Spiegelman, PhD, directed the research that led to this new discovery. We talked with Dr. Rosenzweig about these new findings.

Q: Just to clarify, what type of exercise are you talking about in this study?

Dr. Rosenzweig: We did this study in mice and most of the exercise consisted of fairly intensive swimming, although we saw similar effects with treadmill running. This is aerobic exercise; the exercise that raises the heart rate. In humans, it might also include bicycling in addition to swimming or running.

Q: Can you briefly describe this research?

Dr. Rosenzweig: We know that exercise does lots of good things for the body's metabolism and skeletal muscle, and that these help prevent heart disease. But we wondered whether it also had direct beneficial effects to the heart. To find out, we studied mice whose hearts had grown bigger in response to exercise (a good type of heart growth), and compared them to mice whose hearts had grown larger due to high pressures in the heart (a bad type of heart growth).

High blood pressure leads to bad outcomes, such as heart failure and dangerous arrhythmias. We wanted to find out why there was this difference in these two types of heart growth. So we used a system that was developed in Dr. Spiegelman's laboratory to characterize every one of the approximately 2,000 genes that act as master control switches and could be involved in these processes.

Q: What did you find?

Dr. Rosenzweig: Our experiments showed that aerobic exercise affects a genetic switch that helps the heart to function better and makes it resistant to heart failure. Interestingly, this same genetic switch appears to increase the division of heart muscle cells. This fact raises the possibility that, one day, we could use this information to help restore damaged heart muscle in patients with heart failure. That possibility is a long way off, but it is something we'd like to work toward.

Q: How do you know that the genetic changes you found actually caused the benefits?

Dr. Rosenzweig: We used an engineered genetic mouse model that "mimicked" the primary genetic change. Interestingly, these mice look like they're conditioned athletes - even though they've never been subjected to any exercise. Their exercise tolerance is better than normal and their hearts function better, as well as being resistant to heart failure.

Q: So if you could find a medicine that does this, then people wouldn't have to exercise?

Dr. Rosenzweig: Well, of course, our goal is not to avoid exercise. As I mentioned before, exercise does lots of good things for your body, and it's unlikely that this one genetic change would give you all of those benefits. But, if we can better understand how this works, we may be able to help patients who can't exercise, or those who already have heart failure. In addition, the suggestion that this genetic pathway may control the growth of new heart muscle cells is an exciting one that someday might help us repair damaged hearts.

Q: What will be the next steps in this research?

Dr. Rosenzweig: We want to understand better how this pathway protects the heart, and we already have some clues. We also want to determine whether this pathway can create new heart muscle cells adequate to repair an injured heart. We are currently creating new genetic models to sort these issues out.

Q: What's your favorite exercise?

Dr. Rosenzweig: I run quite a bit - but not because it's my favorite, it's just most convenient. I think keeping active at whatever level you can and with whatever activity works for you is very important for all of us. This latest research is just one more reason to keep going!

Above content provided by Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.

Posted February 2011

Contact Information

CardioVascular Institute at
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215