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Gene Therapy Creates Healthy Heart Muscle

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart.  Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Todd K. Rosengart, from Baylor College of Medicine (Texas, USA), and colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material.  The GMT genes alone reduced the amount of scar tissue by half (as compared to animals that did not receive the genes), and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes.  The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.  Submitting that “This experiment is a proof of principle,” the study authors conclude that: “[Vascular endothelial growth factor] administration to infarcted myocardium enhances the efficacy of GMT‐mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.”

Megumi Mathison, Robert P. Gersch, Ahmed Nasser, Sarit Lilo, Mallory Korman, Todd K. Rosengart, et al.  “In Vivo Cardiac Cellular Reprogramming Efficacy Is Enhanced by Angiogenic Preconditioning of the Infarcted Myocardium With Vascular Endothelial Growth Factor.”  J Am Heart Assoc., December 19, 2012.

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