NEW YORK (Reuters Health) - Rats with chronic heart failure following myocardial infarction show beneficial effects from gene therapy with a modified form of phospholamban, a protein that regulates the calcium pump in cardiac muscle cells.
In a paper in the March 1 issue of the Journal of Clinical Investigation, an international team led by Dr. Yoshitaka Iwanega of the University of California, San Diego in La Jolla, California, describes experiments using a rat model of post-infarction chronic heart failure.
In the treatment group, the researchers inhibited the activity of phospholamban by delivering a pseudophosphorylated mutant form of phospholamban, S16EPLN, into failing hearts 5 weeks after myocardial infarction by transcoronary gene transfer via a viral vector.
At 2 and 6 months after gene transfer, the treated animals had a higher mean left ventricular ejection fraction and less of an increase in left ventricular end-diastolic pressure compared to control animals treated only with saline; in those animals, progressive deterioration was noted.
Furthermore, at 6 months, the treated rats also had better left ventricular function, as determined by contractility and relaxation, as well as lower left ventricular mass, smaller myocytes, and less fibrosis than the control animals.
The researchers note that in failing cardiac muscle, there is downregulation of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2). This enzyme plays a major role in the contraction-relaxation cycle and in transporting calcium into the sarcoplasmic reticulum. A press release from the publishers of the journal explains, “The presence of S16EPLN upregulated the activity of...SERCA2...and compensated for defects in calcium uptake during heart failure.
“Our findings of enhanced function, reduced remodeling and fibrosis, and lessened heart failure in an animal model relevant to the setting of heart failure in patients after a large acute myocardial infarction lend support to the potential therapeutic usefulness of this gene transfer approach,” the investigators conclude.
Source: J Clin Invest 2004;113:727-736 [ Google search on this article ]
MeSH Headings:Biological Therapy: Genetic Engineering: Genetic Techniques: Investigative Techniques: Therapeutics: Gene Therapy: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
