Gene transfer improves function of aging hearts in animals

etimes into the lungs. Heart failure is a growing health problem in the developed world, with more than 400,000 people being diagnosed in the U.S. each year. While deaths from coronary heart disease have decreased in recent years, heart failure deaths are on the rise - more than doubling from 1979 to 1995.

With true heart failure, the weakened heart muscle functions poorly throughout the entire heartbeat cycle - both in the contraction (systolic) phase and in the relaxation (diastolic) phase. However, in a significant number of older people (40 percent of those over 60), the heart contracts normally but the relaxation phase is abnormal, a problem called diastolic dysfunction. These patients exhibit some symptoms of congestive heart failure and many proceed to the complete syndrome.

It is well known that failing hearts do not properly handle calcium, a mineral that plays a key role in the contraction of any muscle cell. Inside the cell, calcium is stored in a structure called the sarcoplasmic reticulum (SR); when it is released in response to the appropriate signals, calcium causes muscle cells to contract. After contraction, calcium returns to the SR via a molecular calcium pump, the SERCA2a protein. Earlier research at the MGH and elsewhere strongly suggested that decreased function of the SERCA2a pump was linked to heart failure and to diastolic dysfunction. While recent studies support the hypothesis that increasing expression of the SERCA2a gene could improve the function of a failing heart, whether the same strategy could alleviate diastolic dysfunction had not yet been tested.

In the current study, additional copies of the SERCA2a gene inserted into a standard experimental viral vector were delivered directly into the hearts of aged rats (26 months old) via a surgically implanted catheter. Three other groups of rats were used for comparison purposes: aged rats that underwent a similar operation without receiving a vector; aged rats tha

Contact: Susan McGreevey
Massachusetts General Hospital

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