New Insights into Preventing Heart Failure
Faculty Profile: Jeff Molkentin, Molecular Cardiovascular Biology
By defining the key molecular signaling pathways in genes that regulate heart hypertrophy, researchers in the Cincinnati Children's Division of Molecular Cardiovascular Biology hope to find new ways to prevent heart failure. Led by Jeffery Molkentin, PhD, these efforts are aimed at understanding and learning how to modify the heart's hypertrophic response.
Although children born with a single ventricular defect usually undergo surgery to correct the abnormality, they remain at high risk of developing and eventually dying of heart failure. A common cause of disability and death among adults, heart failure is a complex disease process that is preceded by cardiac hypertrophy, ventricular remodeling or ischemic disease with or without cellular death.
As the heart responds to its environment, it senses when its output is insufficient for the body's demands. To compensate, the heart increases in size; this response is hypertrophy. Dr. Molkentin's laboratory focuses on studying what makes the heart get bigger. It is known that the body secretes neuroendocrine factors to cause the enlargement; receptors on cells then stimulate signaling pathways. The researchers have shown that one particular signaling pathway -- the calcineurin-NFAT pathway, previously defined by Dr. Molkentin -- can be central to the hypertrophic process.
New work in the lab is revealing that when the enzyme PKC-α is deficient in mice, the heart functions better because it can resist insults that would otherwise cause heart failure. Because this type of enzyme, a kinase, is a relatively easy target for drug development, it could provide a novel target for drug design to combat heart failure.
In addition to multiple NIH awards, the success in Dr. Molkentin's laboratory has merited an agreement with Procter & Gamble Pharmaceuticals, Inc., which will help to support the lab's work over the next three years. The funding will enable the lab to pursue additional avenues of research, and could lead to a potential intellectual property agreement with P&G to protect and develop lead molecules or targets for heart failure discovered by the lab.
