Sep. 29, 1997 University of Maryland researchers have confirmed the link between a calcium-handling enzyme and the strength of the heart’s beat. They also have been able to enhance the heart’s beating strength, using a genetically altered adenovirus (the virus that causes colds) to give heart muscle cells additional copies of the gene that produces the crucial enzyme.
Their research could pave the way for gene therapy in certain kinds of heart failure, repealing a death sentence for many. Cardiovascular diseases are the leading cause of death in the population as a whole.
Dr. Guiseppe Inesi and Dr. Terry Rogers will present their findings to a New York Academy of Sciences meeting on September 29 at the Hyatt Regency on Capitol Hill in Washington, DC. Inesi is professor and chairman of the Department of Biochemistry and Molecular Biology at the University of Maryland School of Medicine, where Rogers is a professor of biochemistry and molecular biology.
During the four-day meeting, scientists from a variety of disciplines will review progress in characterizing the underlying mechanisms of heart failure, examine unresolved questions, and discuss potential therapies.
The Maryland researchers made their discovery from two complementary experiments. Using thapsigargin—a substance extracted from a Mediterranean plant—to block the enzyme ATPase (adenosine triphosphatase) in heart muscle cells, Inesi and colleagues caused a marked weakening of contractions. Since ATPase is an enzyme that regulates the flow of positively charged calcium ions through heart muscle cells, the experiment showed that the calcium movements sustained by this enzyme are vital to the development of a strong heart beat.
"We observed a marked reduction of intracellular calcium ion transients and a negative effect on muscle contraction, demonstrating the prominent role of the calcium-handling ATPase in the contraction-relaxation cycle," Inesi said.
In a related experiment, the Maryland researchers altered an adenovirus so that it can’t reproduce. Then, using recombinant DNA techniques, they turned it into an efficient vehicle for transporting additional copies of the ATPase gene into heart muscle cells. This gene-copy enrichment resulted in a marked increase in the ability of the cells to control intracellular movements of calcium ions and to develop contractile strength—a strong heart beat.
"The complementary experiments with thapsigargin and recombinant adenovirus demonstrate that the calcium-handling ATPase is a crucial enzyme in regulation of contractile strength in heart muscle," said Inesi. "The conceptual understanding and the techniques established by this work are an important step in the possible development of gene therapy for certain types of heart failure."
The research was funded by the National Institutes of Health.
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