|Carly Knazze, a member of the U-M womens track team, is a sophomore from Southfield. Runners like Knazze have a secret weaponhigh levels of a protein called parvalbumin in their skeletal muscle. Photo by Martin Vloet, U-M Photo Services|
This protein, called parvalbumin, helps skeletal muscle fibers in the arms and legs contract and relax rapidly and efficiently. Olympic sprinters have high levels of parvalbumin in their skeletal muscle, which helps explain why they can run faster than the rest of us, according to Joseph M. Metzger, associate professor of physiology and of internal medicine. Parvalbumin works like a sponge, helping skeletal muscle cells relax faster by soaking up calcium ions.
In a study published in the Jan. 15 issue of the Journal of Clinical Investigation, Metzger and a team of U-M researchers show for the first time that parvalbumin also can improve heart function in laboratory ratsrestoring normal relaxation rates in hearts with a condition that mimics the abnormally slow cardiac relaxation common in human heart failure.
Although important and challenging scientific obstacles remain, our findings raise the intriguing possibility of one day using parvalbumin therapy to treat progressive heart failure in humans, Metzger says.
Exacerbated by high-fat diets and not enough exercise, heart failure is a growing medical problem affecting approximately 5 million Americans, with more than 700,000 new cases reported each year. About 40 percent of the time, heart failure is associated with a condition called diastolic dysfunction, in which the heart contracts normally but doesnt relax fast enough to allow the cardiac chambers to fill with blood before the next contraction.
In a healthy, living heart, all cells work together like an orchestra with one conductor, Metzger says. In a heart with diastolic dysfunction, the cells relax too slowly, so the heart pumps inefficiently, and body tissues are starved for oxygen.
The gene for parvalbumin is found in every cell in the body, but it is not naturally activated or expressed in heart muscle cells. To test the proteins ability to relax cardiac muscle, U-M researchers used a common adenovirus to deliver human parvalbumin genetic material into heart cells of laboratory rats used in the study.
In three separate experiments, all reported in the Clinical Investigation article, U-M researchers found that:
This was a proof-of-principle, short-term study, Metzger says. Since adenoviral vectors elicit an immune response after about six days in animals, they arent suitable for this application in humans, where parvalbumin must be expressed for long periods of time. There are many new adenoviral-related vectors in development, however, which could be just as effective without provoking an immune response.
The U-M study was funded with grants from the American Heart Association, the National Institutes of Health, the Culpepper Foundation and the U-M Center for Integrative Genomics. The U-M has applied for a patent on the technology.
Michael Szatkowski, a senior research fellow in the Medical School and a neonatology fellow at Thomas Jefferson University in Philadelphia, is first author on the paper. Other U-M collaborators include Margaret V. Westfall, assistant professor of physiology and surgery; Carly A. Gomez, clinical assistant professor of pediatrics and communicable diseases; Philip A. Wahr, assistant research scientist; graduate students Daniel E. Michele and Christiana Dello-Russo; and research associates Immanuel I. Turner, Katie E. Hong and Faris P. Albayya.