March 26, 2004

Activity of calcium-handling gene appears to prevent cardiac arrhythmias

Activation of a gene that can correct heart failure by improving calcium metabolism may also help prevent arrhythmias, sometimes-dangerous disturbances in heart rhythm, according to a study from the MGH Cardiovascular Research Center (CVRC) The article in Proceedings of the National Academy of Sciences describes how overexpression of the gene for SERCA2a in the hearts of rats reduced arrhythmia after heart muscle injury.

"If these results hold up, SERCA2a gene therapy could help protect patients at risk of arrhythmia from existing heart disease or prevent rhythm disturbances that can occur after cardiac procedures," says Roger J. Hajjar, MD, of the CVRC and the MGH Heart Failure Center, the paper's senior author.

Contraction of any muscle cell requires the correct movement of calcium within the cell. In heart failure the heart muscle is weak and does not pump effectively, partially because SERCA2a, which helps transport calcium between cellular structures, functions poorly. Earlier animal studies by the same CVRC team — led by Federica del Monte, MD, PhD — have confirmed that increasing the expression of SERCA2a could correct heart failure.

In anticipation of clinical trials, a concern was raised that SERCA2a's action could stimulate arrhythmias, a possibility the current study was conducted to investigate. The researchers used standard gene therapy techniques to induce overproduction of SERCA2a in the hearts of normal rats. Two control groups received other genes. Several days later, each rat had one of its coronary arteries tied off and then reopened, producing the kind of heart-muscle injury that can occur with a heart attack.

Contrary to the researchers' earlier concerns, the rats whose hearts overexpressed SERCA2a had less arrhythmia during and after cardiac injury than did the control rats. In addition, the injured area of heart muscle, corresponding with tissue destroyed in a heart attack, was smaller with expression of SERCA2a. In addition to Hajjar and del Monte, the study's authors include Djamel Lebeche, PhD, Luis Guerrero, and Tsuyoshi Tsuji of the CVRC.