Protein Sustains Both a Sound Mind and a Strong Heart

 Mens sana in corpore sano" is a Latin aphorism written by the Roman poet Juvenal, usually translated as "a sound mind in a sound body." Juvenal made an early connection between the relationship of a sound mind and a sound body. However, a new study from John Hopkins explains the link between the two could be biochemical, and not merely coincidental.

There is a possible biochemical link between depression and heart disease, two disorders that often occur in tandem, but with a relationship that remains poorly understood.

The study, published in Proceedings of the National Academy of Sciences, reveals that a protein, already known to act as a natural antidepressant, enhance learning and memory, stimulates nerve cell growth and nourish blood vessels, is also a key player in maintaining heart muscle vitality.

The research team conducted experiments in mice and lab-grown heart cells, findings of which showed the multi-tasking protein - a nerve-growth factor called BDNF (brain-derived neurotrophic factor) - helps sustain the ability of heart muscle cells to contract and relax properly.

The results of the research, indicate that BDNF can precipitate heart muscle dysfunction and has a role in a cascade of molecular signaling events in heart cells, the disruption of which leads to heart muscle failure.

Heart failure affects nearly 6 million Americans and more than 23 million people worldwide. If the study is confirmed in humans, the finding could pave the way for new treatments for certain forms of heart failure.

Single multi-tasking protein affects 'many organs and functions'

BDNF is known for having antidepressant effects and boosting nerve cell health. Results suggest a possible biochemical link between depression and heart disease, two disorders that often occur in tandem, but with a relationship that remains poorly understood.

The research team at the Johns Hopkins University School of Medicine in Baltimore, MD, says:

"Our results are not only a vivid reminder of the astounding complexity of the heart's chemistry and physiology, but also a striking example of the ability of a single protein to act on multiple fronts and affect many organs and functions."

Also clarified by the findings is the biological means behind recent and unexplained observations, which heart failure patients, whose cardiac function worsens during physical exertion, have low levels of BDNF in the blood.

Their observation that BDNF directly controls the ability of heart muscle cells to 'beat' properly offers one possible explanation behind the declining cardiac function seen in people with heart failure, especially during exercise.

Initial experiments, by the scientists, consisted of isolating cardiac cells from rodents with either normal or failing hearts in a lab dish and exposing the cells to BDNF.

Cardiac cells from rodents with normal hearts responded by contracting and relaxing vigorously in the presence of BDNF. Cardiac cells obtained from failing hearts, even when awash in BDNF, responded weakly or not at all.

The team set out to determine why the cells responded in such a way by homing in on BDNF's receptor, a molecule called TrkB, located on the surface of cells and responsible for receiving BDNF's chemical signals and transmitting them inside the cell.

TrkB receptors from mice with normal hearts were compared with those from the failing hearts, results showed that the failing heart cells displayed a slightly different version of the TrkB receptor. The main difference being that it produces less of a catalyst protein responsible for triggering critical signaling inside the cardiac cell.

The inefficient version of the TrkB receptor was less responsive to BDNF, rendering the cardiac cell less sensitive to the protein. While this TrkB variant is fairly common and does not necessarily predict disease, it may render the heart cells of those who carry the altered version less capable of using BDNF.

Mice engineered to carry the ineffective TrkB receptors in their cardiac cells developed impaired cardiac function - the hearts contracted poorly, pumped blood less efficiently and took additional time to relax after every beat.

"Taken together, these findings show that any abnormality in the way BDNF communicates with its receptor appears to unlock a cascade of chemical glitches that eventually leads to poor cardiac function."

Signaling disruptions explain chemotherapy-induced heart failure

These disruptions in efficient BDNF-TrkB signaling can also explain the force behind chemotherapy-induced heart failure, a serious side effect of certain cancer treatments. Such treatments contain chemicals that block multiple growth-factor receptors, including TrkB, to bring tumor growth to a halt.

While this approach is essential to keep cancer progression at bay, interfering with the ability of cardiac cells to respond to BDNF can inadvertently lead to heart failure.

The investigators identify that low BDNF levels alone may not be sufficient to cause immediate heart disease. However, chronic BDNF deficiency or insensitivity, compounded by additional physiologic or pathologic stressors, is a main culprit in fueling the disease.

In the absence of chronic stressors, such as hypertension or an elevated workload of the heart muscle, BDNF deficiency may not cause full-blown disease, but it could be the proverbial straw that leads to a 'broken heart.

References:

John Hopkins Medicine news release, accessed 13 January 2015, via Newswise.