Myocardial Biology/Heart Failure

Myocardial Biology/Heart Failure

Heart failure means that that the heart is not pumping as it should. It doesn’t mean the heart stops, but rather, that over time it loses pumping function, causing fatigue and shortness of breath. It’s something nearly 5 million Americans face. Understanding the cellular basis of heart failure before and after it happens, along with genetic mutations and differences in men and women, helps researchers target research and create clinical trials. The innovative new methods researched ultimately impact patient care.

Understanding the Cellular Basis of Heart Failure

For instance, it may sound counterintuitive, but researchers at Johns Hopkins say that disrupting the electrical activation of the heart for a few hours a day may be exactly what it needs to avoid heart failure — it actually makes the heart stronger. Similarly, understanding the cellular basis of heart attack and heart failure by researching how modifying calcium, nitric oxide, reactive oxygen species, intermediate filaments and proteins such as CamKII, PDE-9 and PKG can forge new ways to treat the failing heart. Besides leading to drug therapies, these advances are leading to biological treatments, where targeting antibodies or specific genes can be introduced to alter heart muscle behavior in ways that counter the underlying disease.

Genetics, Sex and Heart Failure

Fruit flies aren’t the first thing to come to mind when thinking of muscles, but researchers are using them to study the heart. Drosophila melanogaster, the fruit fly, expresses heart and skeletal muscle much like that found in humans — in fact, made up of much the same protein building blocks. Humans with mutations in a single molecule in a muscle protein can develop severe heart disease. Researchers are using the fly heart to study how this happens and then testing drugs that might fix it.

Our clinical researchers are learning about the abnormal right heart in diseases where pressures in blood vessels of the lung increase greatly. Women and men are different in many ways, and heart failure is one of them. We are studying heart failure in women, notably after menopause, to discern how the hormone changes impact pathways that contribute to this disease and specific ways this could be targeted by therapies.

Regenerative Therapies

Many new methods are being researched once a patient has already had heart failure or a heart attack. We are identifying new protein pathways that are abnormally active in the diseased heart and finding new ways to counter them. Stem cell and regenerative therapies for heart failure and heart attack include using cells derived from human blood or skin that are changed to a heart stem cell. Laboratories are developing methods to implant these stem cells into the heart, including implantable bioreactors to keep them active and tissues printed by a biological 3-D printer. 

Videos

#TomorrowsDiscoveries: Preventing Heart Failure – David Kass, M.D.

Over the course of his 30 years at Johns Hopkins, David Kass, M.D., has worked to understand why the heart fails and what we can do about it. He and his team developed a pacemaker-like treatment that coordinates the heartbeat. Called cardiac resynchronization, this treatment is now used worldwide.

#TomorrowsDiscoveries: Heart Attack in a Dish – Dr. Brian O’Rourke

Dr. Brian O’Rourke and his laboratory study how mitochondria, the cellular powerhouses of the heart, contribute to heart attacks and heart failure.

Researchers