Of Mice and Men (and Effects of Gene Silencing)

In this issue of Circulation, Zheng and coworkers1 demon-strate the efficacy of specific small interfering RNAs (siRNAs) added to University of Wisconsin solution in protecting donor hearts against cold ischemic injury during storage and subsequent reperfusion. siRNAs targeted tumor necrosis factor-, C3, and Fas. The study design was well rationalized and performed systematically to confirm the efficacy of these siRNA constructs in silencing their respec-tive targets, first in cell culture and subsequently in whole mouse hearts. Quantitative polymerase chain reaction was used to demonstrate knockdown of each of these proteins after ischemia and reperfusion in contrast to their strong upregulation in control hearts. Beneficial effects were con-firmed by enhanced function, decreased apoptosis, dimin-ished neutrophil activation and infiltration, and less histolog-ical evidence of tissue damage in the treated hearts.