When a person has a heart attack, portions of the heart muscle die in the next several days or even weeks if deprived of oxygen for long enough. The recovering heart slowly remodels itself, even fostering the growth of new blood vessels, in an attempt to regain some of its former function. But all too often, the remodeling is actually harmful, and the damaged heart is on an inevitable downward slide to heart failure.
Now, scientists at the Center for Translational Medicine at Temple University School of Medicine have identified a key target they hope will help stave off the potentially harmful effects of remodeling. They have shown that by turning off the activity of a protein, GSK-3α, in the heart cells of mice that have had a heart attack, they can prevent heart remodeling, preserve heart function and significantly improve survival.
Their findings offer new insights into processes underlying remodeling, and perhaps to eventual strategies against heart failure. They reported their results November 5, 2012, at the Late-Breaking Basic Science Oral Session at the American Heart Association's Scientific Sessions 2012 in Los Angeles.
"We need to find ways to prevent and slow down remodeling of the heart after a heart attack - that's the Holy Grail of heart failure," said senior author Thomas Force, MD, Professor of Medicine and Clinical Director of Temple's Center for Translational Medicine. "Our findings are important steps in understanding some of the mechanisms at play in remodeling, and hold promise to eventually lead to new interventions and perhaps even help prevent heart failure."
Focusing on GSK-3α
The protein enzyme GSK3 - glycogen synthase kinase 3 - plays a key part in many cellular processes and diseases. It has two forms, GSK-3α and GSK-3β, both of which have particularly important roles in heart disease. While the exact role of GSK-3α in heart cells has been unclear, studies indicate that it is important in regulating the heart's growth, ability to contract, and its expansion in size associated with heart disease and heart failure.
To find out the role of GSK-3α specifically in heart cells, Dr. Force, first author Firdos Ahmad, PhD, a postdoctoral fellow in the Department of Pharmacology and the Center for Translational Medicine and their co-workers compared mice with normal levels of the protein in their heart cells to mice with heart cells lacking a working GSK-3α. All of the mice in both groups experienced the equivalent of a heart attack. The researchers found that the mice missing the protein in their heart cells had significantly better survival (100 percent) over the next several days or week compared to the normal mice (75 percent survival).