The Investigation
The current investigation involves Mayo Clinic patients who suffer from a severe heart disease known as "idiopathic dilated cardiomyopathy," which leaves the heart highly vulnerable to failure under stress. The cause is unknown, but the usual heart disease risk factors physicians look for -- high blood pressure, elevated cholesterol, smoking, obesity -- are not necessarily present. To the researchers, this suggested problems in this patient group that had been missed by the standard screening for heart disease: defects in the heart's stress management system.
Looking for Clues in Heart Patients' DNA
To get data from patients, Dr. Terzic's team collaborated with Timothy Olson, M.D., who directs the Mayo Clinic Cardiovascular Genetics Laboratory. Dr. Olson is a leader in identifying hereditary factors that cause heart disease. With the permission of selected patients who suffered heart failure of unknown origin, he carried out extensive genetic scans of DNA obtained from blood samples. Results showed that some patients shared a defect in a gene that makes a stress-reaction-type protein.
Says Dr. Olson: "By introducing a conceptually new mechanism for heart failure, our work points out how molecular genetics can provide a very powerful tool to diagnose a defect in a specific protein in a human disease." Several genes contribute to the heart's ability to adapt to stress. Mayo will be conducting further genomics and proteomics studies to help understand their role in heart failure and enable improved treatment.
After finding mutations, researchers reproduced the mutations in the laboratory using recombinant genetic techniques that allowed them to observe the molecular consequences of the mutations. They found that the mutations create an abnormality within vital structures of heart cells known as the ATP-sensitive potassium channel.
Potassium C
'"/>
Contact: Bob Nellis
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
29-Mar-2004